Propolis is a natural resin produced by Africanized honeybees and stingless bees (SB), playing an essential role in the protection and organization of colonies. In the genus Melipona, this material is known as geopropolis, as it results from the combination of plant resins, waxes, salivary secretions, and inorganic materials such as soil and/or clay. This complex matrix acts in sealing crevices, reinforcing nest structure, mummifying intruders, and maintaining an aseptic internal environment, thereby contributing to colony health (Cardozo et al., 2015; Sousa et al., 2019).

Since antiquity, bee products have been used in traditional medicine, mainly due to their therapeutic properties. Among these products, geopropolis has attracted increasing scientific interest because of the wide range of biological activities attributed to it, including antioxidant (De Souza et al., 2013; Dutra et al., 2014), anti-inflammatory (Franchin et al., 2012; 2013), gastroprotective (Ribeiro-Junior et al., 2015), antiviral (Coelho et al., 2015), antimicrobial (Sousa et al., 2019; Novaes & Torres, 2024), and antiproliferative activities (Cunha et al., 2013; Campos et al., 2014). Despite this potential, systematic studies on Brazilian geopropolis only began in the late 1990s, which explains the still limited knowledge regarding its chemical composition, biosafety, pharmacological properties, and possible biomarkers (Bankova et al., 1998; Cardozo et al., 2015).

The chemical composition of (geo)propolis is notoriously complex and variable, being influenced by factors such as surrounding vegetation, seasonality, climatic conditions, soil type, and the genetic characteristics of the producing bees. In the case of stingless bees, this variability is even more pronounced due to the high diversity of species and the scarcity of consolidated data on the botanical sources exploited, which hinders the detailed chemical characterization of this matrix (Menezes, 2005).

Previous studies have reported the presence of different classes of organic substances in the geopropolis of Melipona species, including prenylated benzophenones, phenolic compounds, di- and triterpenes, free and glycosylated flavonoids, phenolic acids, terpenic acids, saponins, aldehydes, and alcohols, as well as minerals derived from the soil incorporated into the matrix (Cardozo et al., 2015; Sousa et al., 2019; Silva et al., 2020). However, there are still few studies that systematically address the isolation, structural elucidation, and biological evaluation of the compounds responsible for the pharmacological activities attributed to geopropolis, especially that produced by Melipona mondury (Dos Santos et al., 2017; Dos Santos et al., 2025).

In this context, the isolation and characterization of bioactive compounds from geopropolis are fundamental strategies to correlate specific metabolites with their possible botanical sources, thereby expanding the understanding of the plants visited by bees during resin collection. Moreover, the identification of these substances allows a more accurate assessment of their biological and biotechnological properties, providing support for the standardization of geopropolis, the establishment of quality and safety criteria, and its potential therapeutic and industrial applications.

Advancing the chemical knowledge of geopropolis may also guide sustainable hive management practices and encourage the conservation of resin-producing plant species, promoting benefits for both biodiversity and meliponiculturists. However, the isolation of substances from this natural matrix poses significant challenges, as geopropolis is produced in limited quantities and exhibits high compositional variability, which hampers the reproducibility of isolation processes and the acquisition of sufficient amounts for structural and pharmacological studies (Magalhães & Venturieri, 2010; Gemim & Silva, 2017).

Given these limitations, the synthesis of natural products and their analogues emerges as a strategic alternative in Natural Products Chemistry, enabling the production of larger quantities of bioactive compounds and the introduction of structural modifications aimed at studying structure–activity relationships. In this regard, chalcones—recognized as biosynthetic precursors of flavonoids and characterized by broad structural versatility and biological relevance—are promising synthetic models for investigating the mechanisms underlying the observed activities.

Accordingly, this thesis is organized into two chapters. Chapter 1 addresses the isolation, chemical characterization, and evaluation of the biological properties of substances obtained from the geopropolis of the stingless bee Melipona mondury, collected in Bosque da Barra, Rio de Janeiro State, Brazil. Chapter 2 focuses on the synthesis of chalcones analogous to the flavonoids isolated from this matrix, aiming to investigate structure–activity relationships and to broaden the understanding of the mechanisms associated with the observed biological activities.

This work describes the phytochemical study of leaves of Ouratea polygyna Engl., that belong to Ochnaceae family. The plant material was collected at the Vale do Rio Doce Natural Reserve (RNV), in Linhares-ES and registered in the RNV herbarium. The crude extract of the leaves was prepared by maceration at room temperature with P.A methanol and concentrated in a rotary evaporator. The crude extract was partitioned with different organic solvents: hexane, dichloromethane, ethyl acetate and methanol, generating their respective partitions. From the hexane partition, were isolated the substances friedelin (1) and β-sitosterol (2). From the dichloromethane partition, were isolated the substances 7,7’’,4’’’-tri-O-methyl-lanaraflavone (3) and 3-β-O-β-Dglucopyranosyl sitosterol (4). From the ethyl acetate partition, amentoflavone (5), 5,4'- dihydroxy-6,7,3',6'-tetramethoxyisoflavone (6), lanceoloside A (7), a mixture of (7+8), being (8) the glycosylated derivative of benzoic acid and 3'-O-β-D-glucopyranosyl-5- hydroxy-6,7,4',5'-tetramethoxyisoflavone (9). All substances were elucidated through analysis of one-dimensional and two-dimensional 1H and 13C Nuclear Magnetic Resonance experiments and comparison with literature data. The substances 7,7’’,4’’’- tri-O-methyl-lanaraflavone (3), 5,4’-dihydroxy-6,7,3’,6’-tetramethoxy-isoflavone (6) and 3’-O-β-D-glucopyranosyl-5-hydroxy-6,7,4’,5’-tetramethoxyisoflavone (9) have not been found in the literature to date. Amentoflavone was tested in Huh-7 cell line for hepatocarcinoma and larvicidal activity against Aedes Aegypti and the glycosylated substances were investigated in silico for action on the 3CLPRO protein of SARS-COV- 2

Biodiesel is a renewable alternative to fossil diesel and has been progressively incorporated into the energy matrix. Its synthesis mainly occurs through the transesterification reaction of vegetable oils with short-chain alcohols, in the presence of catalysts. Homogeneous basic catalysts, such as NaOH and NaOCH3, are widely used, but some drawbacks have motivated the study of heterogeneous catalysts, such as CaO. This work investigates the influence of alkaline salts on the conversion of biodiesel synthesis catalyzed by quicklime. The reaction was carried out at 60 °C for 120 minutes, with and without the additives CH3CO2Na, CH3CO2K, NaCl, and KCl A total of 45.0 g of soybean oil, 1.6 g of quicklime (both calcined and uncalcined), 3.0 mmol of additive, and a molar ratio of methanol:oil of 4:1 were used. A factorial design 2³ with a central point, using CH3CO2Na and calcined lime, evaluated the effects of reaction time (60 and 180 min), additive percentage (0.17 %m/m and 0.93 %m/m), and catalyst percentage (1.7 %m/m and 5.3 %m/m). The conversion with uncalcined lime was 45%, increasing to 93.7%, 91.3% and 62.0% with the additives CH3CO2Na, CH3CO2K, and NaCl, respectively. The addition of KCl reduced the conversion to 17%. Calcining the lime increased the conversion to 72%. With the calcined lime and additives, the conversions were 92.4% (CH3CO2Na), 93.5% (CH3CO2K), 93.7% (NaCl), and 90.2% (KCl). It was observed, through the conversions, that CH3CO2Na and CH3CO2K allow to forgo calcination. The conversions obtained in the factorial design varied from 77.59% to 92.95%. The three main effects and the time*additive and time*catalyst interactions were statistically significant (α = 0.05). The maximum conversion (92.95%) was achieved with 5.3 %m/m of catalyst and 0.93 %m/m of additive, after 60 minutes of reaction, at a molar ratio of methanol:oil 4:1.

Dengue is an arbovirus endemic to tropical and subtropical regions. The incidence of dengue has increased in recent decades, particularly due to climate change. This represents a serious public health problem, exacerbated by the lack of licensed antivirals. Nonstructural protein 5 (NS5), which acts as an RNA-dependent RNA polymerase (RdRp), is essential for viral replication. It is highly conserved across serotypes and has no homologues in humans, making it a strategic target for drug development. In this study, we applied a virtual screening approach based on structure docking to identify ligands for the allosteric N site of NS5. A novel, non-commercial chemical library consisting of 657 compounds derived from dissertations and theses from the Graduate Program in Chemistry at UFRRJ was used. The screening was conducted with the GOLD 2023.2.0 program, ChemPLP scoring function, using the ensemble docking technique. The scores obtained were normalized by molecular mass and surface area to select fragments (mass <300 Da) and by √N (number of non-hydrogen atoms) to reduce bias related to molecular size. Twenty-three compounds were selected, 17 fragments and 5 larger molecules. Cinnamic acid, the best fragment in the mass criterion, was optimized by fragment growth techniques, generating the ligand (E)-3-(3-(2-carboxyvinyl)phenoxy)benzoic acid as the most promising derivative. The larger compounds stood out for establishing relevant interactions with key residues of the site, such as Arg729, Thr794, Trp795, and His800, including hydrogen bonds and cation–π interactions. Interaction enthalpies were estimated using the semiempirical PM7 method (MOPAC2016), considering implicit solvent, revealing very interesting values, up to -96 kcal/mol for (E)-3-(3-(2-carboxyvinyl)phenoxy)benzoic acid, which exceeds the value of the reference inhibitors. Among the larger compounds, two fully comply with Lipinski's rules, suggesting potential for oral administration and predicted toxicity comparable to or better than that of known inhibitors. In this context, the PPGQ2000701 series stands out. Fragment optimization also led to an improvement in the pharmacokinetic profile, eliminating the predicted interaction with CYPs. The results indicate that compounds from the PPGQ-UFRRJ library are promising candidates for DENV NS5 inhibitors and promising starting structures for rational drug design. Furthermore, FBDD techniques proved effective in improving the interaction and pharmacokinetic profiles of the ligands.

The perovskite structure is recognized for its remarkable properties in solidmaterial chemistry. Recently, research has focused on high-performance photocatalytic technologies for environmental recovery and sustainable energy generation. Rhodamine 6G (Rh-6G) is a widely used synthetic dye, but it is poorly biodegradable and polluting. When released into water, it can harm aquatic fauna and flora. Due to its stability and toxicity, it is frequently studied in photodegradation to reduce environmental impacts. Interest in photocatalysis has driven studies of perovskites such as NaNbO₃, KNbO₃, and LiNbO₃, due to their photocatalytic properties and band gap tunability. In this work, the modification of LiNbO₃ with silver was evaluated on the photocatalytic efficiency to degrade Rhodamine 6G under visible light. The photocatalytic capabilities of LiNbO₃ and Li(1-x)Ag(x)NbO₃ perovskites with silver concentrations of 5%, 10%, 20%, 30% and 40% in mol were analyzed. Photodegradation of Rh-6G was performed under visible light, using a xenon lamp (300W, 400nm filter) or blue LED (10W, 440nm). The dye calibration curve was constructed to determine the molar absorptivity coefficient, with maximum absorbance at 526nm. A concentration of 10mgL⁻¹ was used, followed by adsorption in the dark for 2h. Photocatalysis occurred under visible light for 120min, with measurements every 15min. Modification of LiNbO₃ with silver increased the photocatalytic capacity, reducing the band gap from 4.10 eV to 2.65–2.82 eV, facilitating electronic excitation. The insertion of silver into the LiNbO₃ structure made the material more reactive, achieving approximately 76% degradation in 120 minutes under irradiation with a xenon lamp and approximately 97% with a blue LED, in the same time interval. The observed kinetics were pseudo-first order for all materials analyzed, with Ag30% being the most reactive in the established period, with values of k = 0.01093 min⁻¹ for irradiation with a 300 W xenon lamp and k = 0.03644 min⁻¹ for irradiation with a 10 W blue LED. Tests with reactive species scavengers showed that the superoxide radical exerts the greatest effect in preventing photodegradation, both for LiNbO₃ and Ag30%. Conduction-band electrons react with dissolved oxygen, forming superoxide radicals that oxidize the pollutant or generate secondary species that promote its conversion to CO₂ and water. Thus, modifying LiNbO₃ with silver proves an effective strategy for developing photocatalysts for the degradation of organic pollutants in water.

The oxygen evolution reaction (OER) is the rate-limiting step of water electrolysis and is essential for sustainable hydrogen production. In this work, we investigate the OER on the (101) and (100) surfaces of TiO₂ in the anatase phase, using Density Functional Theory (DFT) calculations to determine thermodynamic and kinetic profiles of the reaction. The analysis of the Gibbs free energies showed that the (100) surface presents a lower thermodynamic overpotential (2.32 V), while the (101) surface exhibits a slightly higher value (2.85 V). However, when considering the activation barriers for the elementary steps of the OER, it was observed that the (101) surface has lower energy barriers, ranging from 0.87 eV to 1.18 eV, while, on the (100) surface, these barriers are significantly higher, reaching up to 2.84 eV. The absence of an activation barrier in the formation of the OOH* intermediate on the (101) surface is one of the factors that favor its greater catalytic efficiency. The scaling relationship between the OOH* and OH* intermediates was analyzed, indicating that the free energy difference between these intermediates remains close to 3.2 eV, which imposes an intrinsic limitation on the catalytic performance. The overestimation of the energy of the O₂* intermediate in the DFT calculations was corrected by adopting an adjustment based on the expected thermodynamic value for the formation of molecular oxygen (4.92 eV), avoiding distortions in the energy profile of the reaction. The results indicate that the isolated evaluation of the thermodynamic overpotential can lead to inaccurate conclusions about the catalytic efficiency, reinforcing the need to also consider the kinetic aspects of the reaction. Thus, the (101) surface of anatase TiO₂ stands out as the most efficient for OER, providing valuable information for the rational design of new catalytic materials aiming at optimizing the energy conversion in electrochemical devices.

This thesis integrates a phytochemical study and evaluation of some biological activities of two Neotropical species: Galianthe matogrossiana E.L. Cabral (Rubiaceae) and Crateva tapia L. (Capparaceae). It details the definition of the molecular structure of a new alkaloid isolated from Justicia wasshauseniana Profice (Acanthaceae). In addition to describing the experimental procedures of isolation, the identification of molecular structures of special metabolites are described. Chromatographic techniques and detailed NMR and MS spectral analyses were used in this work. Biological activities such as anti-nociceptive, anti-inflammatory, and antioxidant activities were evaluated. Twenty-one compounds were identified in the nonpolar fractions of roots and aerial parts of G. matogrossiana, including fatty acid, anthraquinone, chalcone and coumarin derivatives, benzoic acid derivatives, steroids, and some pentacyclic triterpenes. In vivo assays (abdominal writhing, formalin, and open field in Swiss mice), with the exception of the hexane root fraction, the other fractions showed strong antinociceptive and anti-inflammatory activity, even superior to morphine. Antioxidant activity, performed in vitro (wild-type and Δyap1 strains of Saccharomyces cerevisiae), revealed that the hexane and dichloromethane fractions are potent radical scavengers. 3O-acetyl oleanolic acid inhibited Trypanosoma cruzi amastigotes (IC50 = 11.06 µM; selectivity = 3.11). Preliminary molecular docking studies suggested promising affinity of triterpenes against Aurora B kinase for anticancer applications. The in vitro antiglycation activity of the crude bark extract of C. tapia was evaluated, but was not very significant. Until now, glycosylated sitosterol and lupeol have been isolated from the dichloromethane fraction. Detailed discussion of the spectrometric data of the alkaloid, previously isolated from J. wasshauseniana, including TD DFT calculations, has defined its molecular structure, including absolute stereochemistry, which was named as "Brazoid E". These results provide insight into the phytochemical composition and biological activities of species with no record study in the literature.

Aedes aegypti is the primary vector of arboviruses with major public health impact, such as dengue, Zika, chikungunya, and Mayaro fever, being capable of adapting to diverse environments and developing resistance to synthetic insecticides. In this context, natural compounds such as flavonoids emerge as promising alternatives for integrated vector management. Morin hydrate, a plant-derived flavonol, has been investigated for its pharmacological properties, but its effects on insect vectors remain poorly understood. The aim of this study was to comprehensively evaluate the effects of morin hydrate on the energy metabolism and biological parameters of A. aegypti, with emphasis on survival, development, fertility, and vector competence. Laboratory assays were conducted using larvae exposed to the compound at different concentrations and under variable nutritional conditions. Growth, survival, energy reserves, biochemical and metabolomic profiles were assessed, in addition to infection assays with Mayaro virus and complementary toxicity analyses in non-target organisms. The results showed that morin hydrate induces dose-dependent larval mortality, delays development, and reduces female fertility, even when exposure occurs only at juvenile stages. Significant depletion of lipids, carbohydrates, and proteins was observed, associated with alterations in metabolic pathways and the induction of oxidative stress, establishing a physiological state similar to starvation. This energy imbalance persisted into adulthood, impairing reproduction and decreasing vector competence for Mayaro virus. Moreover, toxicity tests in mice revealed no relevant adverse effects, supporting the selective and environmentally safe potential of the compound. Collectively, the findings demonstrate that morin hydrate acts as a multifunctional metabolic modulator, simultaneously impairing survival, metabolism, development, and reproduction of A. aegypti, representing a promising alternative for the development of sustainable and selective vector control strategies.

Neurodegenerative diseases, in general, are characterized by progressive loss of vulnerable neurons and are related to conformational abnormalities of proteins, such as the formation of oligomers containing the α-synuclein protein in Parkinson's disease (PD) and the β-amyloid peptide in Alzheimer's disease (AD). The plant C. sativa has a diverse chemical profile depending on its genotype, including various classes of substances such as cannabinoids, flavonoids, terpenes, and alkaloids. However, most research addresses the role of phytocannabinoids in isolation. In this study, we evaluated the effects of four C. sativa extracts with different phytocannabinoid chemical profiles in two cellular models that reproduce alterations in cellular homeostasis common during the cellular phase of PD and AD. We used Saccharomyces cerevisiae strains with a deletion in the Yap1p transcription factor and transformed with plasmid DNA expressing aSyn and Aβ42, as well as genetically modified human cells (H4) expressing aSyn. Phytochemical characterization revealed extracts rich in tetrahydrocannabinol – THC (69.88%), cannabidiol – CBD (52.64%), and cannabinol – CBN (47.38% and 58.64%), and we concluded that, regardless of these percentages, all C. sativa extracts showed antioxidant activity independent of the endogenous antioxidant defense system, and reversed the redox imbalance caused by proteins associated with neurodegenerative diseases. However, the extracts were not able to protect against mitochondrial damage caused by aSyn expression, although they protected mitochondria affected by the Aβ42 peptide, suggesting selectivity towards the expressed protein. Furthermore, the extracts reduced the number of intracellular inclusions in H4 cells and increased the number of inclusion-free cells, demonstrating protective biological activity against toxicity caused by aSyn production in H4 cells. C. sativa extracts showed promising effects in modulating aSyn inclusions and in intracellular antioxidant protection, but their role in mitochondrial regulation still needs further investigation.

Pyrazoles are five-membered aromatic heterocyclic compounds of which three are carbon atoms and the other two are nitrogen atoms that, by convention, assume positions 1 and 2 of the ring. Given its wide spectrum of biological activities reported in the literature, such as analgesic and anti-inflammatory, bactericidal, fungicidal, antiviral, antitumor and others, this class of heterocyclic compounds has aroused the interest of chemical and pharmaceutical industries that continually search for new substances that are potentially more effective in combating diseases and, at the same time, have lower toxicity. Cancer is a disease that is the second cause of death in Brazil and worldwide. Leukemias are a group of malignant neoplasms whose main characteristic is the uncontrolled proliferation of immature hematopoietic progenitor cells. Once produced, these cells accumulate in the bone marrow (BM), causing a series of damages and compromising their normal functions. In this context, using three previously synthesized nitriled precursors (47-49) and four different nucleophiles, this work aimed to prepare a family of ten pyrazoles (53-62), two of which are new (56 and 59). Spectroscopic techniques such as infrared, hydrogen and carbon-13 nuclear magnetic resonance were used to confirm the proposed structures. Once confirmed, the ten structures were subjected to in silico tests using the LCL-Pred and AdmetSAR software in order to carry out screening for subsequent biological evaluation of these compounds. Thus, based on the data generated in this analysis, it was possible to suggest that compounds 53 and 60 would be those most likely to have antitumor activity and at the same time likely to present low toxicity levels. Once selected, these two pyrazoles were subjected to toxicity analyzes using the Artemia salina method and their effects on the viability of Jurkat cancer cells. These studies showed that both had effects on the inhibition of cell viability, with compound 60 being more active. Given the structural similarity between these compounds, with the substituent linked to the pyrazole ring in position 4 being the only difference, it was possible to suggest that the nitrile group plays an important role in this mechanism of action on the cancer cells evaluated.

The use of plant-derived allelochemicals has emerged as a promising alternative for insect
control, owing to their non-toxicity to humans and the environment. Morin, a flavonoid
primarily extracted from plants of the Moraceae family, has exhibited a wide range of
applications in model organisms. This compound has demonstrated efficacy in inhibiting fatty
acid synthase and ecdysone 20-monooxygenase, enzymes crucial for the insect life cycle. Fatty
acid synthase plays a fundamental role in lipid metabolism, synthesizing long-chain fatty acids
from Malonyl-CoA molecules and forming complex lipids such as triacylglycerols (TAGs). In
insects, this lipid synthesis is critical in various life cycle events including reproduction, flight,
and development. In this study, we investigated the effects of morin ingestion in Aedes aegypti,
the primary vector of several arboviruses, including those causing Dengue, Zika, Chikungunya,
and Yellow Fever. For this purpose, a feeding approach was employed, with mosquitoes being
fed and separated at 24-, 48-, 72-, and 96-hours post-emergence. Additionally, females and
males were kept in separate cages throughout the assay. Through this, it was possible to assess
the TAG content of the whole body and fat body of the insects, along with the relative
expression levels of fatty acid synthase (fas1) and triacylglycerol lipase (tagl1). This approach
revealed that the effects of feeding varied according to the sex and age of the mosquitoes. While
females did not show a reduction in lipid content in the fat body after morin ingestion, males
exhibited lower levels of triacylglycerols. Therefore, we investigated the effects of morin-fed
males on copulation, finding that females mated with treated males laid fewer eggs and had a
reduced hatching rate. In summary, our findings indicate that morin feeding was more effective
in males than in the pre-vitellogenic period of females. The results related to fecundity and
fertility highlight morin as a promising molecule for studies on insect control of interest, both
in public health and agro-economic contexts.

Curcumin (1) is a natural product of the diarylheptanoid class, being the majority component of the Curcuma longa, which presents a wide variety of applications in medicinal
chemistry since antitumor activity, until anti-inflammatory, antioxidant, antiparasitic, among
others that classify it as a multitarget substance. Despite a variety of works in the literature
relating the activity of curcumin (1) against Leshimania amazonensis and Plasmodium
falciparum, there are few reports from studies about its activities against Trypanosoma
cruzi, the etiological agent by Chagas Disease (CD). CD affects approximately 8 million
people worldwide, with only two drugs, benznidazole (7) and nifurtimox (8), available to
treat the patients. Both drugs present low efficacy for long-term treatment and much
systemic toxicity, with collateral severe effects, and only benznidazole is now available in
Brazil. In previous work, the LaQuiMed group was one of the pioneers in researching the
activity of curcumin (1) against T. cruzi (Dm-28c strains), obtaining IC50 values in vitro of
10,13 μM against epimastigotes forms and investigating the interactions with tubulin, by in
silico methods, as its possible molecular target. Thereby, this work's objective is to
synthesize a series of products planned by medicinal chemistry strategies of non-classic
bioisosterism (33 - 41), like natural curcuminoids (1 - 3) analogs, and molecular
hybridization as hybrids (54 - 56) with nitroimidazoles portions, aiming to enhance the
curcuminoids biological activity against parasite amastigotes forms (intracellular replicative
form), following the in silico investigation of the interactions of the product with its potential
molecular target and pharmacokinetic profile (ADME) to reduce cytotoxic effects
to the host and justify the products selectivity. From that, it was possible to obtain a hit
(compound 33) among ten synthetic derivatives (33 - 41, 55) obtained at this work. The set
of derivatives was tested against mammalian cells (LLC-MK2), which was the host cell
used in the infection protocol. Compound 33 was the most promising one with IC50 of
17,20 ± 4,37 μM against T. cruzi (Tulahuen C2C4 LacZ strain) amastigotes in vitro and
IC50 > 200 μM against host cells, then expressing 11,63 of selectivity index (SI), which is
ten times higher than that observed for curcumin (1) and other natural diarylheptanoids (2
and 3). The in silico studies were accomplished to analyze the product interactions with
tubulin (curcuminoids possible molecular target) of T. cruzi by comparative modeling and
used to investigate the possible action mechanism of products by molecular docking in
tubulin, presenting a good correlation of score results and experimental results (R = -0,76),
being able to demonstrate the mitotic catastrophe process in the parasite caused by the
product's presence. Furthermore, the product's cytotoxicity has been evaluated by
theoretical methods from ADME analysis and by the capacity to suffer Michael's reactions
at the biological environment to justify its interaction with undesirable molecular targets
that could elevate their respective cytotoxicity. These analyses can justify the biological
actions and the selectivity of the hit (33) against the parasite, highlighting it as the primary
hit in this work.

In Brazil there are a variety of species of stingless bees (meliponines), belonging to the Apidade family. The bee Melipona quadrifasciata anthidioides, object of study in this work, is capable of producing geopropolis, a resinous substance with a complex matrix, consisting of a mixture of clay with plant exudates. Several biological activities of geopropolis have been evaluated, such as antibacterial, antifungal, antiviral and antioxidante. Sporotrichosis is an infection caused by the fungus of the genus Sporothrix, being a zoonosis, which in Brazil is endemic and transmitted by the fungus Sporothrix brasilliensis. Treatment options, such as Itraconazole, have been hampered by the emergence of new fungal isolates with drug resistance. Therefore, the search for new substances that can be used in the treatment of sporotrichosis is of scientific interest. This work aimed to evaluate the chemical profile, the content of phenolics and total flavonoids, the antioxidant capacity, isolate and characterize substances from mandaçaia geopropolis (Melipona quadrifasciata anthidioides), in addition to investigating the in vitro antifungal activity against clinical isolates of S. brasiliensis. The geopropolis was collected in Bosque da Barra, Rio de Janeiro, and the ethanolic extract of mandaçaia geopropolis (EEGP-M) was prepared in an ultrasonic bath for two hours. Subsequently, the ethanolic extract was solubilized in methanol: water (7:3 v/v) and partitioned with hexane and dichloromethane, respectively, generating the fractions: Fr. Hex, Fr. DCM and Fr. MeOH:H₂O. Fr. Hex was subjected to open column chromatography on silica gel, where two diterpenes with an ent-kaurene skeleton were isolated, the diterpene kaurenoic acid, and a cinnamic acid derivative, kaur-16-en-19-oic acid, 15-[(1-oxo-3-phenyl-2-propen-1-yl) oxy], furthermore, another diterpene, ent-caurenal, was characterized as an enriched fraction. Total phenolic and flavonoid content was evaluated in comparison to gallic acid (GA) and quercetin (QE) standards, respectively. Fr. DCM obtained the best results, with 1.89 mg E_AG/100mg in phenolics and 0.42 E_QE/100mg in flavonoids. The DPPH assay was used to determine the antioxidant capacity of the extract and its fractions, again the Fr. DCM fraction showed the best result (EC₅₀ = 200 µg/mL), corroborating the results of total phenols and flavonoids. Antifungal activity was investigated against clinical strains of S. brasiliensis.  The best result was observed for the isolated cinnamic acid derivative (MIC = 0.469 mM), however kaurenoic acid (MIC = 1.875 mM) and the fraction enriched with ent-kaurenal aldehyde (0.187 mg/mL) also showed good results; among the ethanolic extract and its fractions, Fr. Hex showed the best antifungal response (MIC= 0.281 mg/mL). The antifungal activity test demonstrated the inhibition potential of the ethanolic extract, its fractions and substances isolated from mandaçaia geopropolis against S. brasilliensis, signaling that this natural product is promising for the treatment of sporotrichosis

Currently 55 million people live with dementia worldwide with nearly 10 million new cases every year. Dementia results from a variety of diseases that affect the brain, and its most common form is the Alzheimer’s disease (AD). AD is driven by multiple deleterious factors, among them, the presence of insoluble filaments and protein aggregates. The inhibition of GSK-3β, a kinase involved in many of these deleterious factors, have shown promising results in vivo, emerging as a promising potentially disease-modifying therapeutic class for AD. So, in this work, we designed three series of 1,2,4-triazoles as GSK-3β inhibitors. The synthetic routes to obtain the designed compounds were sucessfully developed. The compounds were tested in vitro against GSK-3β and the results are promissing, with the discover of a hit compound. In addition, the series with best profile was used in the design and synthesis of a new series of GSK-3β degraders (PROTACs).
In parallel to the pharmacological work, we developed the synthesis procedure and molecular diversity exploration of the 1,2,4-triazole nucleus through metal-catalyzed cross-coupling reactions, in addition to a copper-catalyzed cyanation reaction using a non-toxic cyanide source in aqueous medium.

Multicomponent Reactions (MCRs) are a set of chemical reactions that have as a general concept the synthesis of a single final product with a high degree of chemical diversity from three or more reagents. Various multicomponent reactions are known, with the main ones being the Hantzsch reaction and the Biginelli reaction. The Hantzsch reaction was originally developed for the synthesis of dihydropyridines; however, after modifications, it has also been used for the synthesis of acridinones. The Biginelli reaction originally describes the synthesis of dihydropyrimidinones, but with a change in reagents, it can also be carried out for the synthesis of quinazolinones. This work demonstrates the use of both multicomponent reactions for the synthesis of a diverse range of heterocycles. A total of 17 acridinones and 7 acridinediones were synthesized through a modified methodology of the Hantzsch reaction. Various reagents were used, demonstrating the versatility of the reaction, yielding 8 novel molecules in the literature. The Biginelli reaction was employed in the synthesis of 11 quinazolinones, with two being novel, and 4 xanthenediones, confirmed as byproducts of the Biginelli reaction. Various reagents were used, showcasing how this reaction can be utilized as a tool in the synthesis of heterocycles. Fifteen acridones were evaluated against targets related to Alzheimer’s disease (cholinesterases and antioxidant activity). The molecules mostly demonstrated inhibitory activity against acetylcholinesterase and butyrylcholinesterase, as well as antioxidant properties, while the permeability across the blood-brain barrier was satisfactory for 8 acridones. The quinazolinones were evaluated for their cytotoxic potential and trypanocide activity. The results indicate promising trypanocide activity for molecules containing the 4-bromophenyl group, while the cytotoxic activity was not satisfactory. Seven acridinediones and two acridinones were evaluated using in silico methods for their potential interactions with tubulin; the results allowed for mapping the interactions that occur when using lawsone as a reagent in the reaction, in addition to demonstrating the modification of positioning at the colchicine site when increasing the size of the acridones. Nevertheless, the overall results appear promising from the perspective of exploratory chemistry, with 39 molecules synthesized through multicomponent reactions. The use of multicomponent reactions has proven to be a fast, effective, and versatile method as a synthesis strategy for new bioactive molecules, contributing to future research.

Green propolis has proven pharmacological properties, such as antivirais, anti-inflammatory and antioxidant action. In view of the SARS-CoV-2 pandemic, its use has gained prominence as a potential therapeutic approach, especially with innovative forms such as orodispersible films. The present study aimed to investigate the chemical composition of Brazilian green propolis, evaluate its antiviral activity against SARS-CoV-2 in vitro and develop an orodispersible film from this extract. 

Ultrasound-assisted extraction, maceration and percolation methods followed by identification by high-performance liquid chromatography with a diode array detector (HPLC-DAD), quantification of total phenolics, total flavonoids and antioxidant activity were also analyzed. The interaction of the bioactive compounds present in the extracts with the SARS-CoV-2 Spike RBD protein and the ACE2 receptor and proteases PLpro and 3CLpro, as well as cytotoxicity assays, were also analyzed. Finally, the formulation of an orodispersive film was performed, where the characterization was performed through analyses of weight uniformity, swelling capacity, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), x-ray diffraction (XRD) and gravimetric analysis (TGA). 

The results showed that the green propolis extracts presented a significant inhibitory activity against the viral enzymes PLpro (64.96% - 93.16%), 3CLpro (0 - 76.79%) and Spike protein (26.42% - 96.41%), indicating its potential as an antiviral agent. These results were related to the compounds identified in the green propolis extracts (Chlorogenic, Caffeic, p-Coumaric, Ferulic, Rosmarinic Acids, Kaempferol, Kaempferide, Artepellina C, Drupamine, Baccharin, Chromene, Pinobanksin). The optimization of the ultrasound extraction methods resulted in high levels of phenolic compounds (76.34% - 75.96%) and flavonoids (29.81% - 27.80%), correlated with the antioxidant capacity of the extracts: DPPH (IC50 4.08 - 4.15) and FRAP (1492.14% - 1450.31%). The orodispersible films developed demonstrated good uniformity and swelling capacity for controlled release of bioactive compounds, suggesting a new form of administration for antiviral treatments. The FTIR, SEM and DRX characterizations 

indicated interaction between the polymer and the extract components, however without the formation of new bonds and with uniformity on the surface. In the TGA it was possible to observe small changes in thermal stability attributed to the presence of the extracts. 

This study highlights the relevance of green propolis as a promising source of compounds with antiviral activity against SARS-CoV-2, in addition to presenting a new pharmaceutical formulation that can be explored in future research. The combination of optimized extraction methods and the development of orodispersible films opens new possibilities for the use of natural products in antiviral therapy. 

At the end of 2019, the world experienced a new viral disease, currently called COVID-19, caused by the coronavirus SARS-CoV-2. COVID-19 has spread rapidly around the world, causing more than 6.94 million deaths to date. Among the proteins of SARS-CoV-2, Spike has aroused special interest, since the coronavirus uses it to bind through the receptor binding domain (RBD) to the converting enzyme of human angiotensin 2 (hACE2), thus initiating invasion into the host cell. A recent in vitro study demonstrated that hACE2-derived peptides containing the amino acid sequence EDLFYQ (SAP1, SAP2 and SAP6) are able to inhibit Spike-mediated viral infection. The objective of this project is to employ theoretical methods to investigate the interaction mode of these peptides with Spike’s RBD, in order to obtain information for the rational design of new peptides, candidates for SARS-CoV-2 infection inhibitors, exploring the covalent inhibition strategy. Because it involves the formation of covalent bonds, the study was conducted using the semi-empirical quantum method PM7, which is fast enough to be applied to whole proteins and their complexes. All calculations involved the complete RBD, using the continuum approach to include the effect of the external environment on energy minimization, without structural constraints. The proposal of the new peptides was based on the chemistry of sulfur-triazole exchange (SuTEx), which allows selectivity for the formation of covalent bonds with tyrosine residues. The SAPs were modified by the incorporation of warhead groups sulfonyl-triazole, and a new proposed warhead group, phosphonyl-triazole, in order to increase the efficiency of the interaction through covalent bond formation. ΔHint calculated correlated with experimentally determined Kd for SAP1, SAP2 and SAP6, and confirm the SAP1 peptide both in native and in SuTEx-type modifications as best candidates for RBD ligands, followed by SAPs 6 and 2, in this order. It was also observed that the covalent complexes formed by SAP1 derivatives containing sulfonyl-triazole warhead groups have a greater tendency to be formed in the medium in which they were studied than those containing phosphonyl-triazole warheads.

Curcuma zedoaria, commonly known as zedoary, is a plant belonging to the Zingiberaceae family, native to India. It is currently cultivated in Brazil and in countries in South and Southwest Asia. In this study, the bioinsecticidal potential of the essential oil (EO) extracted from the rhizomes of C. zedoaria(Zingiberaceae) was evaluated. The EO was obtained by hydrodistillation (3h) and identified by GC/MS. The yield was 0.15%, and the three main chemical constituents found were 1,8-cineole (24.11%), camphor (12.13%), and curzerenone (9.68%). In the bioassays conducted for the reproductive stages of the flea C. felis felis, using the filter paper impregnation method, with final concentrations of C. zedoariaEO ranging from 10 to 1000 μg.cm-2. The results showed that adult fleas exhibited 100% mortality starting from the concentration of 800 μg.cm-2at 24h and 48h, differing from the pupal stages with 94.23% mortality at the concentration of 396 μg.cm-2, larvae with 100% mortality at the concentration of 117.5 μg.cm-2at 24h and 48h, and eggs with 98% mortality at the concentration of 396 μg.cm-2. Regarding the inhibitory action of C. zedoariaEO on the acetylcholinesterase enzyme, as verified through the modified Ellman method, it was observed that the activity observed, using the EO, when compared to the control, demonstrated low inhibition, as the oil inhibited approximately 20% of the enzymatic activity, even at its highest concentration. In toxicity assays using the yeast S. cerevisiaeas a research model, it was observed that C. zedoariaEO exhibited high toxicity, as the assay resulted in mitochondrial damage, thus impairing cellular development. Further studies are required, as despite showing bioinsecticidal potential against different developmental stages of the flea C. felis felis, the EO proved to be toxic in the assays conducted with the yeast S. cerevisiae.

From observational research, about 204 complex organic molecules have been detected in interstellar and circumstellar medium. Furthermore, a diversity of organic compounds, including biomolecules, has been identified in fragments of comets and meteorites. Among such biomolecules, sugars and their precursors are of special interest. The general objectives of this work are: to investigate reaction mechanisms, not yet elucidated and under astrochemical conditions for the abiotic synthesis of the sugar precursors: glycolaldehyde (GLA), glyceraldehyde (GLI) and dihydroxyacetone (DI) in gaseous phase and on surfaces . The mechanism of GLA synthesis in the gas phase was investigated at CCSD(T)/M06-2X/aug-cc-pVTZ level, considering the elementary reactions: R1: CO + CH3OH, R2: H2O + CH2CO, R3: HCO + CH2OH , R4: OH + CH2CHO and R5: H2CO + trans-HCOH, all leading to the formation of GLA, the R5 route being possible in two ways: the first through the abstraction of the hydrogen of O-H from trans-HCOH by the carbonyl oxygen (R5a ), with an energy barrier of 10.1 kcal/mol; and the second way by the abstraction of the hydrogen of C-H from trans-HCOH by the carbonyl carbon (R5b), in a reaction without a barrier. Rate coefficients, obtained in the range of 10 - 500 K, are expressed by: kR1(T) = 1,8010-15 T0,7exp ( -86,11/RT), kR2(T) = 5,1910-14 T-0,12exp (-78,76/RT), kR3(T) = 3,6610-17 T2,18exp (-0,22/RT), kR4(T) = 2,9010-16 T2,11exp (-0,12/RT), kR5a(T) = 1,3410-9 T-1,93exp (-9,57/RT)andkR5b(T) = 8,7110-17 T2,17exp (0,03/RT). Rate coefficient calculations suggest that the barrier-free pathways R3, R4, and R5b are the most likely pathways for glycolaldehyde formation. A better distinction of R3, R4 and R5b occurs at high temperatures (~500 K), where R4 is the fastest. Rate coefficients for R4 decrease significantly with the lowering of the temperature and, around 100 K, route R5b shows the highest rate coefficient, being indicated as the most probable route of GLA synthesis, in colder conditions. Route R5b was extended to the formation of glyceraldehyde (trans-HCOH + GLA → GLI) and R5a to the formation of dihydroxyacetone (trans-HCOH + GLA → DI), showing rate coefficients expressed by: kR5b-GLI(T) = 6,4310-18 T2,18exp (0,12/RT)and kR5a-DI(T) = 6,7710-18 T1,98exp (-0,08/RT), in the range of 10 to 500 K. It is known that heterogeneous reactions, on surfaces of astrochemical grains, play an important role in the synthesis of compounds of increasing molecular complexity. Thus, the R5 reaction was also studied on a forsterite surface and periodic calculations at PBE level, adopting Vanderbilt ultrasoft pseudopotentials (USPP), suggest that formaldehyde and trans-hydroxymethylene reagents are adsorbed on the surface, reacting by Langmuir–Hinshelwood mechanism , in a similar way to R5a, leading to the formation of glycolaldehyde, which is strongly adsorbed, with adsorption energy equal to -205.03 kcal/mol. The intense adsorption of this precursor should allow consecutive reactions, leading to an increase in the complexity of surface sugars. Finally, this study allowed conclusions about the possible routes of abiotic synthesis of glycolaldehyde, glyceraldehyde and dihydroxyacetone.

Unconventional Food Plants is the term used to refer to a group of plants that have one or more edible parts, whether native or cultivated, and are not part of the daily diet of the population. An example of this is Xanthosoma sagittifolium L. Schott (taro), where studies point to a range of potential activities attributed to this plant, such as anti-inflammatory, antidiabetic, and antioxidant properties. The chemical characterization of Xanthosoma sagittifolium L. Schott describes the presence of flavonoids. Therefore, when introduced into the diet, it can assist the body in maintaining cellular redox homeostasis, helping to prevent oxidative stress, which is a condition caused by the inability of the antioxidant defense system to control the action of oxidants in cells, which can lead to various damages. However, it is important to delve more deeply into the compounds present in this plant and to analyze in more detail the influence of its antioxidant activity using a biological model that takes into account physiological conditions and metabolic interactions. Thus, the toxicity and antioxidant potential of the aqueous extract of X. sagittifolium were evaluated through cell viability assays, mitochondrial functionality, lipid peroxidation, and intracellular oxidation levels. Two strains of S. cerevisiae were used in this study, one control and one with a deletion in the YAP1 gene, a transcription factor for antioxidant defenses in yeast. The chemical profile of the aqueous extract of X. sagittifolium was verified by HPLC-DAD. All analyzed concentrations of the extract in both strains were not found to be toxic. The analysis of the effect of the extract on cell viability revealed that pretreatment with the extract at a concentration of 0.6 mg L^-1 can provide protection for both strains against the stressor used (H₂O₂) at a concentration of 1.0 mM. In antioxidant assays, for the control strain, the X. sagittifolium extract is capable of providing antioxidant protection to the cells. In contrast, the same was not observed in the mutant strain, where only in viability antioxidant assays was the X. sagittifolium extract able to provide protection to the cells, while in the other antioxidant assays, the strain exhibited a higher degree of sensitivity to oxidative stress. The chemical profile of the extract indicates the presence of flavonoids, accounting for 15 of the 17 peaks obtained in the chromatogram. In this study, it was indicated that the extract was non-toxic at the tested concentrations and exhibited antioxidant properties. These antioxidant properties can be attributed to the presence of flavonoids in the extract, suggesting that taro has the potential to be a promising source of compounds with antioxidant action.

Promising molecular targets for the search for new drugs for diseases such as dengue hemorrhagic fever, cancer, cardiovascular diseases and inflammation are matrix metalloproteases (MMPs), with emphasis on MMP-9, as it plays a central role in hemorrhagic and inflammatory processes and is frequently overexpressed in these pathologies. As there are different classes of MMPs, a central issue in the development of inhibitors of these enzymes is the search for selectivity. This project aims to analyze, using theoretical methods, the selectivity of semicarbazones (SC) and thiosemicarbazones (TSC), previously designed and synthesized by our group, in relation to MMP-9, aiming to design new candidates for selective inhibitors for this enzyme. Furthermore, the study seeks to analyze the pharmacokinetic properties of the most selective compounds using theoretical methods to determine their potential viability for human administration. Molecular docking studies were carried out with the structures of MMP-9 (PDB 6ESM) and MMP-1 (PDB 1HFC), with the Goldscore function. The complexes with the best poses were selected and subjected to geometric optimization via semi-empirical calculations with the PM7 method, adopting the protein in its entirety and in a continuous medium representing the solvent, to determine the interaction enthalpy of the compounds. The results show that ligands from the TSC group, in general, present a promising selectivity profile with human MMP-9, highlighting ligand 23b, which was used as the basis for a new series of more selective ligands. This approach resulted in relevant data on the interaction profile of TSC with the S1' sites of the MMP-1 and MMP-9 enzymes, explored in rational planning aiming at selectivity. The BH series ligands proved to be potentially selective, with emphasis on the BH02a molecule, which showed better interaction performance and selectivity for MMP-9 than 23b. The modifications were found to be beneficial for the predicted ADMET properties.The BH series balances solubility and membrane penetration, with improvements in TSC absorption, although BH02a and BH02b show slightly reduced absorption due to high polarity. Biodisponibility results indicate potential for oral drugs without PAINS alerts. With broad systemic distribution, especially the more lipophilic compounds in the BH series, they show potential for partitioning into lipid-rich regions such as the extracellular matrix. TSC inhibit CYP1A2, with BH01a also inhibiting CYP2C19, suggesting potential drug interactions, but proposed modifications reduced CYP3A4 inhibition. All compounds have low T1/2 and renal clearance, suggesting more frequent administration, and show no apparent cardiotoxicity. BH01a exhibits genotoxicity, and there is a general tendency toward hepatotoxicity, with 25, BH01, and BH01a being less hepatotoxic. TSC meet the FDA's maximum daily dose, indicating safe administration, and compounds 23b, 23c, 25, and the BH series have low acute toxicity, with BH01b, BH02, BH02a, and BH02b being the least toxic.

Neglected diseases are diseases caused by infectious agents and/or parasites and are considered endemic in low-income populations. These diseases have unacceptable indicators and reduced investments in research, drug production and their control, because of this, it is necessary to search for new drugs that cause better treatment for patients, in addition to being less toxic. Among the neglected diseases that will be addressed in this work are Chagas disease, Zika and Chikungunya, diseases with few or no drugs available. Within the context of medicinal chemistry, coordination compounds gained prominence due to their biological applications, for example, the treatment of cancer and arthritis, antimicrobial agents and enzyme inhibitors. Structural knowledge and understanding of the mechanisms of pharmacological action of these compounds are of fundamental importance in the development of new, more efficient and safer drugs for the human body. Coumarin and quinolone derivatives and various metal complexes have been studied for their potential as agents against neglected diseases. Thus, coumarin-imidazopyridine hybrid linkers of the ethyl 2-(R)-2-oxo-2H-chromen-3-yl)imidazo[1,2-a]pyridine-3-carboxylate (R = 7-Et2N) (HL1), 7-OCH3 (HL2), 8-OCH3 (HL3) and 6-CH3 (HL4)) and 2-(R)-2-oxo-2H-chromen-3-yl)imidazo[1,2- a]pyridine (R = 7-OCH3 (HL5), 8-OCH3 (HL6)) plus four quinolone-derived linkers of the 3-carboethoxy-4-oxo-1,4-dihydroquinoline type (R = 6-H (HL7 ), (6-F (HL8), (6-Cl (HL9) and (6-Br (HL10)) were synthesized. Reactions between ligands (HL1-HL6) and zinc chloride resulted in neutral complexes of the type [ZnCl₂(HL1-6)2](C1-C6), and reactions between HL1-HL3 ligands with AgNO₃ resulted in charged complexes [Ag(HL1-3)₂]NO₃ (C1Ag-C3Ag). Syntheses involving Zn(NO₃)₂, phenanthroline and the quinolone-derived ligands (HL7-HL10) resulted in the charged complexes [Zn(phen)(HL7-10)]NO₃ (C7-C10). The crystal structures of the C2 complexes [ZnCl₂(HL₂)₂] and C3 [ZnCl₂(HL₃)₂] were determined by single crystal X-ray diffraction (XRD), which reveals showed the coordination of two ligands through the nitrogen of the imidazopyridine group, with two chlorines completing the metal coordination sphere and thus exhibiting a distorted tetrahedral geometry. In this work, the anti-cruzi, anti-zika and anti-chikungunya evaluation of four pairs of ligands (HL1-HL4) and complexes (C1-C4) was carried out. The anti-t.cruzi evaluation showed that, initially, the C4 complex was the most active molecule, having twice the activity of its corresponding ligand HL4 (12.4 and 22.8 µM), indicating that coordination can be be favoring the biological activity and even helping to make the ligand bioavailable in the biological environment. Furthermore, the antiviral evaluation of the ligands (HL1-HL4) and respective complexes (C1-C4) against Chikungunya (CHIKV) and Zika (ZIKV) showed that, in general, all compounds exhibited excellent antiviral activity, with highlight for the C2-C4 complexes, which were more active for ZIKV than their parent ligands (IC50 C2-C4 = 0.8 µM, IC50 HL2-HL4 between 1.2 and 4.8 µM) and about 4x more active than the Ribavirin control (IC50 = 3.95 mM). Against CHIKV, the HL3 ligand stood out, which exhibited higher activity than the control and very low cytotoxicity (IC50 = 0.67 µM and CC50 = 910 µM vs IC50 Ribavirin = 2.42 uM and CC50 = 297 µM ), resulting in excellent selectivity index (SI). Unlike what was observed for ZIKV, the activity of the ligands did not increase with complexation when it comes to CHIKV, however, all compounds are eligible to have their mechanisms of action studied, which is in progress.

In recent decades, several programs have been developed with the aim of calculating rate coefficients for uni and bimolecular reactions, such as the Multiwell and POLYRATE programs, being the second the most used. Despite the excellent performance of these programs in the calculation of rate coefficients, the need to investigate special cases such as dissociation reactions and complex mechanisms instigate the development of new programs. KINPRO is a package composed of several computational codes in order to perform calculations of kinetic parameters based on the conventional or variational transition state theory. It includes KINP pre-processing facilities plus other programs like KDIS, KUNI and MULTI, as well as KCVT, which is the canonical rate coefficients calculation program. The mechanisms obtained through theoretical calculations of the reaction of 1-pentene + OH radical and the oxidation of dimethylsulfide and its possible products were used to validate these programs. For the description of the mechanisms, GAUSSIAN 09 and ORCA programs were used. The addition of OH radicals to 1-pentene, described at the M06-2X/aug-cc-pVDZ level, allowing the study a small but complex system from the point of view of the multiplicity of conformers and reaction pathways, and to explain the non-Arrhenius behavior of experimentally observed global rate coefficients. Once dimethylsulfide enters the troposphere, it reacts with atmospheric oxidants, such as the OH or O3 radical, the former being described as preferential, due to its higher reactivity. This oxidation leads to the formation of various sulfur products that act as cloud condensation nuclei formers and will directly interfere with the temperature of the region. Therefore, there is a great interest in studies involving accurate forecasting of climatological events and, although there are several experimental works, there is not a wide range of theoretical works in this area. This work aims at developing a mechanism for the reactions between DMS and the OH radical and other sulfur compounds that are formed and to develop the kinetics of these reactions. To create this model, around 67 reactions were selected and theoretical calculations at the M06-2X/aug-cc-pVTZ theory level were made. Among these there are several uni and bimolecular reactions which opens space for a large number of tests. The results suggest that the computational implementations were successful, generating higher quality results than those that had already been calculated. The package is finally recommended for research in Theoretical Chemical Kinetics.

Coffee is the most consumed beverage in the world, and the second most commercialized commodity, generating numerous residues from its processing and consumption. Coffee grounds are the most expressive residue of this production, currently much appreciated for its numerous applications in industry and research, its most valuable component being the oil obtained by extraction with organic solvents. In the present work it is proposed to carry out studies with coffee grounds obtained from two different species (Coffea arabica and Coffea canephora) from the states of São Paulo and Minas Gerais for the extraction of lipids through a Soxhlet extractor using ethanol and n-hexane, after the drying process. The yields obtained from the oil extraction were from 63.83 for the A3E sample to 5.75 for the CH sample. The acid value of the samples ranged from 4.04 mg KOH/g of oil for the 100% Arabica A1 sample to 11.96 mg of KOH/g of oil for the 100% Conilon sample. Given the possibility of obtaining different results for the quantification of fatty acids for the same sample depending on the esterification method used, in this work the acid profile of coffee grounds oil was investigated through three methods involving acid catalysis (BF3/MeOH, and CH3OH/) and basic catalysis (MeONa/MeOH). The main fatty acids identified were palmitic acid (18.50-52.59%), linoleic acid (0-38.18%), oleic acid (2.87-17.69%) and stearic acid (5.49-17.90 %). The contents and chemical profile of fatty acids were obtained by means of gas chromatography with flame ionization detector (GC-DIC) and gas chromatography coupled with mass spectrometry (GC-MS). There were no significant differences in the lipid profile of the samples, regardless of the solvent used, as well as the species originating from the coffee grounds evaluated (Coffea arabica and Coffea canephora). The degree of swelling followed the profile of release of bioactive compounds present in the film and the highest gel fraction was presented by the conillon sample without washing. The films remained with their surface and integrity preserved. And the presence of turbidity and coloration in the solution indicated the presence of bioactive compounds in suspension. The total phenol content in the four analyzed samples ranged from 6.00 ± 0.65 to 7.79 ± 0.58 mg GAE/100mg of sample. The lowest EC50 value was related to the conilon sample. The oil release test in the “peel off” mask showed that the type of coffee, the type of solvent and the washing of the lees significantly interfere with the release of fatty acids, at 232nm Arabica coffee obtained greater release compared to Conilon and at 210nm masks containing Conilon coffee released more than arabica. The wavelength of 210nm (palmitic acid) obtained the best results in the release, and at 232nm (linoleic acid) the release was much lower. In the caffeine and chlorogenic acid release test, sample A2 showed the highest rate of release of both chlorogenic acid (50rpm – 115%, 100rpm – 114.98%) and caffeine (50rpm – 78.22, 100rpm – 61.99), followed by the Conilon sample, 50rpm – 34.81% and 100rpm – 22.40% for the release of chlorogenic acid and 50rpm – 19.88% and 100rpm – 39.65% for caffeine. It was possible to verify the great potential of the solid residue (coffee grounds) obtained daily as a raw material to be used in the cosmetic industry.

Alzheimer's Disease (AD) is a neurodegenerative disorder that affects memory and motor functions, being considered a multifactorial disease of undetermined origin. The main therapeutic strategy for the treatment of AD is the use of anticholinesterase drugs, inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The present work aims at the structural design, synthesis, characterization, in vitro and in silico evaluation of a new series of 1H-indole-2-acylguanidinic derivatives designed as candidates for cholinesterase inhibitors. The proposed derivatives were designed through the bioisosteric exchange of the 4,5-dibromopyrrole nucleus, present in the selective inhibitors of BuChE described in Goulart’s doctoral thesis (2021), by the indole aromatic heterocycle. The synthesis of derivatives was based on obtaining the key intermediate tert-butyl-(1H-indol-2-carboxamido)(methylthio)methylene)carbamate through the reaction between indolic acid chloride and mono-protected isomethylthiourea and later condensation with benzylamines of interest, followed by removal of the protection group in an acidic medium. The products were characterized by ¹H and ¹³C NMR. In vitro screening of AChE and BuChE inhibition highlighted the best products (28c) and (28d) as selective inhibitors of BuChE, which inhibited BuChE activity by more than 60% at a concentration of 30 µM and with an IC₅₀ of 5.997 and 5.498 µM, respectively. The structure-activity relationship corroborated previous results that already pointed to the importance of the free acylguanidine function for the inhibition of BuChE, and also indicates that the presence of bromo substituents in the heteroaromatic ring seems to be important for the activity of these derivatives, which still needs to be proven from the evaluation of brominated indole analogues. Additionally, halogenated substituents on the benzyl ring of acylguanidine favored anti-BuChE activity. Using the SwissADME tool, it was possible to predict that the new acylguanidines have good pharmacokinetic potential. Molecular docking studies carried out made it possible to understand the possible modes of interaction of compounds with BuChE. As perspectives, we have the proposition of new analogues of the series obtained for its optimization, as well as for a better understanding of the structure-activity relationship. The results showed that the structural planning was successful, but there was no optimization regarding the enzymatic activity. As future perspectives, we carry out assays of antioxidant activity and complexation with metals, in addition to proposing new analogues in an attempt to optimize the anti-BuChE activity, as well as for a better understanding of the structure-activity relationship. Additionally, we intend to investigate other pharmacological targets for the indole and dibromopyrrolic acylguanidines.

The interaction between humans and animals has increased more and more, and with that, the
concern for the health of these animals. Cats and dogs are susceptible to
infestation by ticks and fleas, with Rhipicephalussanguineus and
Ctenocephalidesfelisfelis the most common. The cat flea, known as C. felisfelis, is

5

a hematophagous, wingless insect that parasitizes domestic animals, which need
daily food. In this way, animals constantly suffer from skin irritations,
anemia and allergic dermatitis. Faced with the development of resistance of these insects against
to treatment with chemical products, essential oils are shown as alternatives
promising, since they already have described activity against some insects. Knowing this
potential of essential oils, the present work aims to extract the essential oil
of C. pulcherrima, identify its components, evaluate its insecticidal activity against
adult and immature stages of the cat flea. In vitro screening tests were performed,
to evaluate the behavior of fleas against the essential oil, in 10 concentrations
different in the period of 24 and 48 hours using 10 fleas. The technique was used
impregnation on filter paper. The essential oil of C. pulcherrima is rich in germacrene D
(47.04%) and showed activity against C. felis. Against adults, it was possible to observe
mortality of 15% and 40% at 800 μg cm -2 , within 24 and 48 hours, respectively.
Against eggs and pupae, 100% mortality was observed at the maximum concentration (800 μg cm -
two ); against larvae, maximum mortality was observed at 400 μg cm -2 at both times.
tested. The activity of the essential oil was also tested, in two concentrations, in the inhibition
of the enzyme acetylcholinesterase, but it was not possible to observe this inhibition against the two
analyzed concentrations. The essential oil studied showed significant activity both
for adults and the immature stages of C. felis, concluding that it can be a great
candidate for flea control, being used as an alternative to
development of natural pesticides.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease known for memory loss and difficulty with language. A set of pathological factors forms it and among them, the cholinergic deficit and oxidative stress stand out. Oxidative stress is characterized by the imbalance between the generation of free radicals and/ or non-radical reactive species and the action of antioxidant defense systems. Currently, the main treatment for Alzheimer's disease is the use of inhibitors of cholinesterase enzymes. However, due to the multifactorial nature of the disease and the fact that many drug candidates have not been successful, a new approach has emerged, the so-called “multi-target” compounds. Therefore, this work evaluated the antioxidant protection of four new compounds containing the core 3-amino-1,2,4-triazole-N-1,5-trisubstituted cholinesterase inhibitors in two strains of Saccharomyces cerevisiae (BY4741 and ∆gsh1) with oxidative stress induced by hydrogen peroxide. The toxicity of the compounds was initially analyzed through the semi-qualitative assay with resazurin and cell growth curves. Antioxidant assays were TBARS and intracellular oxidation by 2,7'- dichlorofluorescein. In the resazurin assay, there was no toxicity of the compounds in the two strains at concentrations below 250 mM. The growth curves confirmed this non-toxicity in the concentration of 20 µM of the compounds for 24h. In strain BY4741 all compounds reduced MDA levels between 30-40%, however in strain ∆gsh1 only compounds containing phenolic substituents were active (25%). In the evaluation of protection to the intracellular environment, only in the ∆gsh1 strain in the fermentative phase of growth, there was a significant reduction of oxidant species promoted by the compounds, with emphasis on the compound with nitro substituent (27%). In the oxygen consumption test, it was impossible to conclude the substances' mitochondrial protection capacity, since there was no statistical difference between the treatments, in both strains. The results demonstrated that triazoles were not toxic and provided antioxidant protection even in the absence of glutathione in S. cerevisiae cells.

The search for new organic eco-friendly corrosion inhibitors is increasingly necessary, given the high cost caused by corrosion and the existence of highly contaminant conventional inhibitors. Thus, in this dissertation was investigated the anticorrosive effect of the extract in ethanol of the aerial parts of the species Justicia brandegeeana (Acanthaceae), popularly known as red shrimp for carbon steel AISI 1020 in acid medium. Two samples were collected, the first in June 2021 and the second in October 2021 with high moisture content (70% and 69%, respectively) and low yields (4% and 3%, respectively). The extracts of both were analyzed by infrared, where it was noted that seasonality interfered only in the intensity of the bands, preserving the nature of the extracted classes of substances. Polar groups were identified, with the ability to present good corrosion inhibition, such as alcohols, carbonylas of carboxylic esters, and 1H and 13C NMR allowed the identification of the carbohydrate class. For all techniques the concentration of the extract varied in 250, 450, 750, 1000 and 1500 ppm. The electrochemical techniques of electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PP) and linear polarization resistance (LPR) were performed in an OCP of 5400 s and were consistent with each other, showing good corrosion inhibition efficiency for all concentrations studied, also showing that the inhibition efficiency is dependent on the inhibitor concentration. The PP curves also allowed to analyze that the extract is characterized as a mixed inhibitor, with a tendency to the cathodic region. Gravimetric analysis of mass loss allowed an evaluation in greater immersion times of carbon steel in the corrosive medium, which are: 3, 6, 24 and 48 hours. The results showed good corrosion inhibition efficiency for all concentrations evaluated, being more expressive at 1500 ppm with 94% inhibition at 6 h of immersion. All concentrations obtained their maximum efficiency at 6 h, stabilizing at 24 h, with decay at 48 h of immersion. When evaluating the effect of temperature variation, the extract showed good thermal stability, with 82% inhibition at 70 ºC, indicating a physisorption, and the efficiency was corroborated by the physicochemical parameters of Ea, ΔH ǂ e ΔS ǂ . The chelating activity of the extract in ethanol was also investigated against Fe+2 ions, and the extract showed 52% chelating effect, being thus in line with the results obtained by the techniques of evaluation of anticorrosive activity. In addition, the images of the morphology of the metallic surface, generated by scanning electron microscopy (SEM) indicated a surface protection with the presence of the plant extract, thus minimizing the roughness. These results make it possible to consider the ethanol extract of Justicida brandegeeana as an eco-friendly agent efficient in preventing corrosion of carbon steel AISI 1020 in H2SO4 1,0 mol L-1 medium.

Peptides are composed of amino acids linked in sequence and comprise a class of molecules of interest within medicinal chemistry. Both for their high selectivity for specific targets and for the complexity of their structures, which allow them to be applied for different purposes, such as antimicrobials or cell penetrating agents conjugated to drugs. Peptides and conjugates are potentially applicable in areas lacking therapeutic innovation, such as the development of new antibiotics for the treatment of multidrug-resistant bacteria or new chemotherapeutic agents for the treatment of Chagas disease. In this work, three series of cationic amphiphilic peptides are proposed with potential application as antimicrobials and cell penetrating peptides. The peptide-drug conjugation strategy with or without control of drug release in the intracellular environment is also evaluated using peptides of interest within the proposed series and the type II polyroline helix P14LRR, which has been reported as an antimicrobial and cell penetrating peptide. The synthesis of peptides and conjugates involved the use of classical organic synthesis techniques, with optimization of protocols found in the literature, as well as the solid phase peptide synthesis methodology. The drugs linezolid (Lnz) and benznidazole (Bzd) were used for the conjugation strategy. Peptide-drug conjugates connected via a spacer containing a disulfide bond, reducible in the intracellular medium, were evaluated for their chemically induced drug release kinetics. Additionally, the peptides and conjugates were evaluated against Escherichia coli for their antimicrobial activity and insights into the mechanisms of action. The design of the series made it possible to trace a structure-activity relationship, and the peptide Ac-YGRRLLRRLL-NH₂ was identified to be the most promising for this application (MIC = 2 µM). The activity against amastigotes and trypomastigotes of Trypanosoma cruzi was also evaluated. The peptide Ac-YGRRLLRRLLRRLLRRLL-NH₂ showed high effectiveness in inhibiting parasite infection in vitro (EC₅₀ = 299 ± 86 nM). Experiments were also carried out to evaluate the cell penetration potential of the Fl-YGRRLLRRLL-NH₂ peptide and the Lnz-Fl-P14LRR conjugate, both labeled with a fluorescein probe. They used flow cytometry and confocal microscopy techniques to verify the accumulation of compounds in the intracellular environment and, in the case of Lnz-Fl-P14LRR, indicating its placing in lysosomes at the subcellular level.

Glycine, the simplest amino acid, has already been detected in meteoritic and cometary samples. The understanding of its existence in the solid state, in the interstellar medium (ISM) is limited, due the lack of studies concerning its reactivity in this environment. Therefore, this work was developed aiming to investigate, by means of computational
methodologies, the thermodynamic equilibrium of the alpha-, beta- and gamma-glycine polymorphs and their reactivity in the solid-gas interface, in ISM analogous conditions. Computational methodologies were applied adopting the Density Functional Theory, accordingly to the periodic boundary conditions formalism. The PBE functional was adopting with the dispersion correction, D3. The inner electrons were treated with the Vanderbilt Ultrasoft pseudopotentials. Kinetic cutoff energy values were tested and converged to 80 Ry. A k-points sample of the reciprocal lattice of 4 x 2 x 4, 4 x 3 x 4 e 3 x 3 x 4 were assumed for the alpha-, beta- and gamma-glycine, respectively. Vibrational properties were obtained by means of the Density Functional Perturbation Theory. The quasi-harmonic approximation was adopted for the estimation of solid-state thermodynamic properties. Calculated entropy values were slightly lower than experimental findings, with absolute deviations of 5.27, 0.13 and 5.42 J mol -1 K -1 , for the alpha-, beta- and gamma-glycine, respectively, at 298.15 K. The obtained Salpha - Sgamma difference value was of 0.44 J mol -1 K -1 , in good agreement with the experimental value of 0.35 J mol -1 K -1 , at 298.15 K. Gibbs free energy values were obtained in the range between 50 K and 500 K and at ambient pressure, being possible to suggest the correct stability order among the crystalline phase: gamma > alpha > beta. The gamma→alpha phase transition was suggested at 442.55 K, in excellent agreement with the experimental value of 440 K. Sublimation properties were investigated taking in consideration the gas-phase transformations between the zwitterionic glycine, present in the crystalline phase and the gas-phase most stable conformer. These energetic terms were obtained at the CCSD(T)/CBS level. Sublimation temperature values were estimated by means of the Clausius-Clapeyron equation, with a maximum deviation of -5.31 K for the alpha-glycine, in the pressure range between 0.1 and 1 Pa, in comparison with experimental findings. Glycine gas-phase decomposition reactions, forming CO2 and CH3NH2, catalyzed by a (010) alpha-glycine surface, were investigated. For this reason, a
3 x 3 expansion containin 4 glycine layers was considered. A k-point sample of 2 x 2 x 1 was adopted. Decarboxylation reaction proceeded through a 4 steps mechanism, with barrier heights of 30.01, 112.10 and 108.83 kJ mol -1 , respectively. Therefore, the good agreement between computational investigations, reported here, and experimental findings, it is possible to suggest that the solid-solid and solid-gas reactivity model of glycine, proposed here, can be adopted for future investigations of the amino acids reactivity in the ISM.

The possible depletion of fossil fuels, the increase in CO2 emissions, and the growing energy demand have aroused interest in alternative sources of green energy. In this sense, biodiesel, a biofuel from renewable sources, has been used as an alternative to replace petroleum diesel. Research involving its synthesis is constantly advancing with the aim of optimizing more and more the process variables. Most of the studies employ a conventional synthesis methodology where the reactants are mixed with the direct addition of the catalyst/alcohol solution over the oil, under constant stirring and heating. This work sought to investigate and optimize an alternative, unprecedented proposal for the synthesis of methyl biodiesel, in which the gradual addition of soybean oil is carried out over the catalyst/methanol solution (inverted procedure), changing the sequence and speed of addition of the reagents. compared to the conventional methodology. The experiments were promoted at 25.0 °C for a lower energy consumption. The study was conducted using a 24 factorial design aiming at the optimization of the following reaction conditions: type of catalyst (NaOH and NaOCH3); synthesis time (40 and 60 minutes); stirring speed (400 and 600 rpm); and oil addition time in the catalyst/methanol mixture in relation to reaction time (percentage relative time, tR) (60 and 80%). After planning, studies were carried out to achieve greater conversions based on the evaluation of the effect of stirring speed (200, 300, 400, 500 and 600 rpm), tR (20, 40, 60 and 80%) and synthesis in two successive steps of transesterification, additionally, a comparison was made between the conventional and proposed synthesis procedures. The planning indicated that the tR and the time of synthesis were the main factors of influence in the conversion for the studied system. Conversions around 86% were obtained by applying tR of 60% for 60 minutes and 400 rpm with the two catalysts used (NaOH and NaOCH3). The post-planning study demonstrated that the strategy of slow addition of oil over the catalyst/alcohol solution achieved higher conversion averages at room temperature and low stirring speeds (up to 300 rpm) compared to the conventional method. The best condition used was performing the biodiesel synthesis in two transesterification steps of 60 minutes, tR of 20%, stirring speed of 300 rpm and NaOH as catalyst, resulting in a conversion of 96.6%. A high conversion of triglycerides was obtained using the proposed experimental procedure under milder conditions and with lower energy consumption when compared to conventional syntheses under heating. This result makes the new experimental procedure attractive for industrial application, considering that minimal changes in the manufacturing process will be necessary, which can even be compensated in the long term by the lower energy demand. The analysis of acidity index, specific mass, kinematic viscosity and ester content indicated the quality of the resulting biodiesel within the standards established by Brazilian legislation.

More than 100 years after its discovery, Chagas disease still represents a challenge for humanity, since its treatment has serious gaps. In addition to not being satisfactorily effective in the chronic phase of the disease, the drugs used worldwide for its treatment, nifurtimox and benznidazole, cause severe side effects to patients treated with them. Thousands of people die each year due to this disease, which mainly affects tropical regions, such as Brazil. In Brazil, only benznidazole is authorized by the National Health Surveillance Agency (ANVISA) for the treatment of Chagas disease. Thus, it is essential that the scientific community dedicate itself to the search for new drugs for the treatment of Chagas disease, more efficient than the actual. In this sense, beta-lapachone derivatives have emerged as promising compounds, especially the azole derivatives. beta-lapachone is a naphthoquinone, found in several tree and shrub species of the Bignoniaceae family, among them, the ipê. In the last decades, several research groups, especially in Brazil, have been dedicated to the synthesis of beta-lapachone derivatives, to combat several pathogens, including Trypanosoma cruzi, which causes Chagas disease. In this work, 26 imidazole derivatives and 2 oxazole derivatives of beta-lapachone were synthesized, of which 21 are unpublished, in addition, a 2-amine-oxazole derived from ortho-phenanthroline-quinone was synthesized. Among the synthesized compounds, 16 were evaluated in vitro for trypanocidal activity, in addition to beta-lapachone, against the amastigote and trypomastigote forms of T. cruzi. Nine of the evaluated compounds were more active in the tests than beta- lapachone, under the conditions tested, among which, two were more active than the standard drug itself, benznidazole. It was also possible to verify that both present greater selectivity for the parasite than for the host cells. One of these two most active had its mechanism of action under the parasite investigated, and it was found that the main damage caused by the compound in question was in the mitochondria, causing swelling, and a washing aspect, in the organelle. In addition to the valuable results of trypanocidal activity, this work also enabled the development of a new method for the synthesis of 2-amine-oxazoles.

Tuberculosis (TB) infection caused by the microorganism Mycobacterium tuberculosis, is currently one of the infectious diseases with high mortality potential, due to the emergence of strains resistant to the drugs available for treatment. The disease occurs latently, the infected individual will present the symptoms years later, being able to develop the multidrug-resistant type (TB-MDR, of the multidrug-resistant English) and the extensively resistant type (TB-XDR, of the extensively drug-resistant English) these variations of the disease represent a major challenge for public health authorities. Although the Stop-Tuberculosis plan has shown some promising results, the fact is that in the current scenario the global reduction rates for the treatment of TB-MDR / XDR are below 50%, being even lower when the spectrum of drug resistance goes beyond that of TB-XDR. The reduction in health supplies and financing from international agencies, the long treatment and the high incidence of adverse events make the task of combating tuberculosis even more difficult. After more than 40 years of neglect, more attention has recently been given to the need for new drugs to fight the disease. Several research works have been carried out recently with the objective of improving the treatment for TB-MDR / XDR. These researches seek therapeutic alternatives for the development of effective drugs. Thus, the development of new substances for the treatment of infection is of relevant interest in the scientific community. This project aims to develop and evaluate the cytotoxic potential of new quinolinic derivatives resulting / planned from the structural modification of 2-chloro-quinoline-3-carbaldehyde, giving rise to new nitrogen-containing heterocyclic compounds. Planned due to the performance of computational studies in order to discover the possible molecular interaction sites of the derivatives with the enzyme DNA gyrase, related to cell replication, obtaining information on the mechanisms of action of these new compounds.

Propolis is a complex mixture of resinous, gummy and balsamic substances collected by honey bees from any part of the plant tissue, to which bees add salivary secretions, wax and pollen to the final product. Due to the great diversity of Brazilian plant species visited by bees, there is a high variation in the constituent substances of propolis, consequently of their active principles and their coloring. The main vegetable source for the production of propolis from the Southeast region of Brazil is the resin collected from young buds and leaves of Baccharis dracunculifolia L., popularly known as field rosemary. This plant native to Brazil provides high levels of different phenolic substances, such as artepillin C, which is considered a chemical marker for this type of propolis. Flavonoids and phenolic acids are substances derived from the secondary metabolism of plants and correspond to approximately 50% of the constituents of propolis, but this percentage may vary according to the region of product collection. The antioxidant properties of this substance may be associated with phenolic constituents present in its extracts, such as rosmarinic acid and artepelin C. Oxidative stress is related to cardiovascular problems, carcinogenesis and neurodegenerative damage. Reactive oxygen species are generated during cellular respiration leaving mitochondrial DNA vulnerable due to its proximity to the electron transport chain. The mitochondria has some fundamental functions in our organism: cellular respiration, through the electron transport chain; the synthesis of adenosine triphosphate (ATP); the mediation of programmed cell death (apoptosis); and the production of heat; besides having its own DNA (mtDNA). The yeast Saccharomyces cerevisiae is used in experiments as a biological model because it has a cellular organization similar to other eukaryotic cells; its genome fully sequenced; easily grown; low cost. In addition to being optional anaerobics and a model organism for understanding the molecular mechanism of mitochondrial diseases. The objective of this work is to evaluate the antioxidant potential of extracts of green propolis and two of its constituents on mitochondrial activity in S. cerevisiae cells. The results revealed that the treatments, artepillin C, rosmarinic acid and the ethanolic and hexanic extracts, both in the concentration 50 µg.mL-1 , showed a good antioxidant potential, as they were able to decrease lipid peroxidation and increase cell viability in fermentative and non-fermentative medium. The ethanolic extract of green propolis in 50 µg.mL-1 was the only one to contribute positively to the electron transport chain, increasing oxygen consumption during maximum breathing.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has a complex pathogenesis, inducing memory loss and cognitive disorders, which usually present in old age. Coumarins and imidazopyridines (IM) are compounds with wide pharmacological activity and have several promising studies related to the treatment of AD acting on several targets such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), aggregation of β-amyloid plaques (Aβ) and between others. Thus, the general objective of this work is the synthesis of new 3- (imidazo [1,2-a] pyridin-2-yl) -coumarins, based on classic bioisosterism substitutions of 4- (dimethylamino) phenyl by imidazopyridines (IM) as possible cholinesterase inhibitors for possible treatment of AD. The first series is the synthesis of 3- (imidazo [1,2-a] pyridines) -coumarins (66a-d) involving 5 reaction steps. Through the synthesis of 3-acetyl-coumarins (67a-c) (70% to 90% yield) (step 1), α-bromination of 3-acetyl-coumarins (51 to 73% yield) (step 2) , formation of the IM nucleus (64 to 69% yield)(step 3), alkylation of the IMs with a conversion factor of 74% (66a) and 81% (66b) (step 4) and, finally, the amination step with the formation of the final compounds (66a-b). The second series is the synthesis of 3- (imidazo [1,2-a] pyridines-9'-ethylcarboxylate) -coumarins, involving Knoevenagel condensation to form compounds with coumarin nucleus (89) (86% yield) ( 1 step), o-alkylation (93a-d) (yields from 30 to 74%), forming the nuclei of the IMs (102a-d) (yields from 42 to 74%) and amination (103a-d) (yields from 31% to 79%). The compounds obtained were purified and then characterized by spectroscopic techniques (¹H and ¹³C NMR). An initial screening was carried out at a fixed concentration of 30 μM, for two final compounds 66b and 103b, obtained initially by the non-optimized synthetic route, with an enzymatic inhibition of approximately 91.7% (AChE) / 92.4% (BuChE) and 98.1% (AChE) / 88.6% (BuChE), respectively. In addition to the activity, silicon studies of molecular modeling and ADME parameters were carried out. Based on these preliminary results, new compounds are being synthesized, and the IC₅₀ and enzymatic kinetics against cholinesterases will be determined.

Aliphatic ethers have been indicated as a possibility as fuels addictive, with potential to reformulate the energetic matrix. This molecule family has relevancy as much in Atmospheric Chemistry as Combustion Chemistry, and learn its reactivity is important to elucidate its behavior and modulate a precise reactional mechanism. The combustion
mechanism starts by unimolecular and bimolecular reactions with OH radicals, following a hydrogen abstraction mechanism. In a similar way, at an atmospheric system, OH radicals are the mainly precursors of these ethers oxidate processes, by hydrogen abstraction mechanisms. This study, as a continuation of previous works, has focus on elucidate the EVE + OH reaction on purpose to observe the interaction of these radicals with more complex structure of the previous studied ether, now with the possibility of addiction channels besides hydrogen abstraction channels. The theoretical calculations have been realized with M06-2x level and aug-cc-pVTZ basis utilizing ORCA software. In comparison with the literature, this work brings a more detailed approach to the theoretical study. By a conformational analysis together with a Boltzmann’s distribution, 4 conformations have been confirmed relevant to the reaction mechanism, its respective intermediates geometries and its correspondents saddle points, that shown similarities of
extreme importance to the prediction of the reaction mechanism. Its connectivity was confirmed by Intrinsic Reaction Coordinate (IRC) and Scan calculations. Those calculations allowed the proposal of new reaction channels, showing multiple possibilities, setting then a multiconformational multireactional study.

Malaria is an infectious and potentially fatal disease caused by protozoa of the
Plasmodium genus, its main vector of transmission is the bite of the female Anopheles
mosquito. Despite being considered one of the diseases with the greatest impact on
morbidity and mortality in countries located in the tropical and subtropical regions of the
planet, there are still not many treatment alternatives that use effective drugs, with low
toxicity and that did not present cases of resistance. Multicomponent reactions (MCR)
are a powerful tool in the search for new drug candidates due to their display of
advantages compared to conventional linear syntheses, and for following principles of
Green Chemistry. Dihydropyrimidinones (DHPMs), products of Biginelli's MCR, are N-
heterocyclic systems that have several pharmacological properties and an easily
reproducible synthetic route, enabling the production of a library of structurally distinct
molecules that can exhibit bioactivity or be modified for this purpose. In this work,
twenty-two DHMPs and nine Quinazolinones were synthesized, five of which were new,
through the use of functionalized derivatives in Biginelli's RMC, allowing the creation of
a library of molecules with different structures and possible antimalarial activity. The
methodology used proved to be effective and simple, allowing the use of readily
commercially accessible reagents, which allowed the synthesis of different compounds
with yields ranging from 15 to 88%. Tests to verify the potential biological activity of the
products obtained are in progress.

Hybrid compounds such as isatin-thiosemicarbazones are found in the literature as substances with great biological potential, such as antibacterial, antitumor, antifungal, among others. However, there are several procedures by which isatin and thiosemicarbazones are combined to synthesize the desired hybrid products. In this work, 18 (eighteen) precursors 4-X-phenyl-thiosemicarbazones and 3-X-phenyl-thiosemicarbazones with different substituents on the aromatic ring were synthesized, where X =H, Cl, Br, F, OCH₃, N(CH₃)₂, OH, CF₃, CH₃, NO₂. Subsequently, 18 (eighteen) new hybrid derivatives were obtained through the reaction of these thiosemicarbazones with isatin. All compounds were properly characterized through routine spectroscopic techniques, the thiosemicarbazones only with IR, as their structures are described in the literature, and the final products were unpublished through the techniques of IR, ¹H and ¹³C NMR. Isatin-thiosemicarbazones were tested for antifungal activity, using the Radial Growth techniques with Aspergillus parasiticus and Minimum Inhibitory Growth (MIC) with Sporothrix schenkii, showing very satisfactory results. The investigation of the structure-activity correlation was carried out using data from the electronic and hydrophobic effects of the synthesized molecules. Finally, the final products were investigated for their chelating effect with iron (II) ions.

The widespread use of pesticides in agriculture has contributed significantly to the increase of environmental contamination. In Brazil, where glyphosate (GPS) responds to the majority of the herbicide consumption, GPS is associated to the contamination of soil and hydric bodies. The Layered Double Hydroxides (LDHs), materials of the anionic clay family, present a high capacity of anions intercalation and they can be used in different segments, such as in the adsorption process and slow release of chemical compounds. Therefore, the aim of this paper was to study the adsorption of the glyphosate pesticide, using calcined LDHs – the so-called Layered Double Oxydes (LDOs) and their process of release by the hybrid material. The studies of glyphosate adsorption in pH 10, using LDO in the proportion 2:1 de Mg/Al, indicated that the process follows a pseudo first-order kinetic, being the Langmuir isotherm model the one that best presented adjustment when compared to the Freundlich and Temkin models. The negative values of ΔG° and positive ΔS° indicate the spontaneity of the adsorptive process. The glyphosate/adsorption interaction mechanism was studied through the powder XRD, ATR-FTIR and NMR of solid 13C and 31P. The 7,4 Å value obtained to the interlamellar spacing suggests that the adsorption does not involve the intercalation of glyphosate, but it does for the hydroxide anion. The band shift in ATR-FTIR, from carboxylate and phosphate portions, to lower numbers of wave on the hybrid compound face the non-adsorbed glyphosate, indicates that these groups are involved in the interaction process of glyphosate/layered of the LDH. As of the 13C {1H} CP-MAS and 31P{1H} CP-MAS spectra, it was possible to infer that the glyphosate is possibly found complexed to the present metals in the LDH lamellas. The study of anionic competition indicates that the increase on the carbonate concentration leads to a significant reduction on the glyphosate adsorption, reaching up to less than 15% when the carbonate concentration is 200 μg/mL. For the release studies, LDHs were synthesized on the Mg-Al-glyphosate system (metallic reason 2:1) by the direct co-precipitation method, followed by reflux and by the reconstruction method, followed by the hydrothermal treatment. The analysis of powder XRD of hybrid compounds suggested that the synthesized material by reconstruction presents a less amorphous character than the one synthesized by co-precipitation and the basal spacing value of 7,8 Å is an indication of interspersed glyphosates on the vertical position. The analysis of ATR-FTIR and NMR of hybrid compounds indicated that the glyphosate interacts with the layered through the carboxylate and phosphate groups, as in the adsorption. To a 48 hour contact time, the glyphosate release was more effective to the pH values equal to 8 and 10, being superior to 70%. To the acid pH 6 and 4, the values were inferior to 60%. A comparative analysis of the glyphosate release face to solutions of nitrate anions, carbonate and chloride, all of them in the concentration of 5 x 10-3 M, indicated that more than 60% of the present glyphosate on the hybrid compound was released after 15 hours when in presence of carbonate. In the solution of the other anions, the release did not exceed 35% on the same period of time. It was observed that, in an aqueous medium, the glyphosate release is directly proportional to the carbonate concentration.

Chagas disease (CD) is a neglected tropical disease caused by the parasite Trypanosoma cruzi and presents millions of cases in several countries. Currently there are no vaccines for CD prevention and there are only two drugs for its treatment, but in Brazil, only benzonidazole is used and is ineffective on disease’s chronic phase. Thus, research for new drugs becomes essential. The enzyme sterol 14α-desmethylase (CYP51) belongs to the ergosterol biosynthesis pathway, which are fundamental for the integrity of the T. cruzi’s cell membrane. Its inhibition causes the parasite’s death and it can be promoted by the coordination of heterocyclic compounds with the iron atom of the enzyme’s heme group. On a previous work, a theoretical model of activity prediction for new inhibitors of CYP51 (T. cruzi), based on experimental and theoretical parameters calculated by molecular modeling, which was used for design new triazole piperine derivatives. On this current work, the original theoretical model was optimized using the semi-empirical PM7 method instead of PM6 and a selectivity study was done by molecular docking of heterocyclic compounds in T. cruzi’s CYP51 and H. sapiens’s CYP51. The most promising compounds, planned by the original model, were synthesized, evaluated in vitro against T. cruzi and they were tested for CYP51 inhibition. The new model presented a multiple correlation coefficient (r² = 0.86) slightly higher than the original (r² = 0.83). The docking study indicates a likely selectivity of the compounds for the parasite’s enzyme. The compounds showed activities against trypomastigote forms with IC₅₀ between 6.13 µM (B2) and 27.59 µM (B11), in agreement with the general predictions made by the model, and low cytotoxicity in primate cells (between IC₅₀ = 15.75 and >50 µM). Preliminary enzyme inhibition assays indicated that the compounds designed with the model are in fact capable of inhibiting the parasite's CYP51.  

lethal, and its triple negative subtype has the highest mortality rate. There is no specific treatment
for the triple negative subtype, and the high rates of disease recurrence and metastasis make it
necessary to search for new forms of treatment. A multicomponent reaction is a type of reaction
for chemical synthesis, where three or more reagents react to form a single product with a high
degree of chemical diversity, and the Hantzsch reaction is one of the first reactions of this type
reported. In the present work, a series of molecules were synthesized, based on the Hantzsch
reaction, and similar in structure to natural products such as Colchicine and Podophyllotoxin
(which have proven antiproliferative activities), which aim to be an optimization of the prototype
LDQMC-014 (7-(3,4,5-trimethoxyphenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one),
the results of which in previous work demonstrate good cytotoxic activity in vitro, having a
satisfactory tubulin polymerization inhibition profile (widely validated target as anticancer).
Varied yields were obtained with confirmation oh the structure by carbon and hydrogen NMR.
Since LDQMC-014 obtained satisfactory results, it was sought to optimize the synthesis results.
Systematic changes were made in the synthesis parameters, which promoted an increase of more
than 78 % in the reaction yield. The enantiomers of LDQMC-014 were separated by chiral
chromatography, which provided good enantiomeric separation, which subsequently allowed
the determination of the absolute configuration of the asymmetric center present by circular
dichroism. Once the enantiomers were isolated, their biological evaluations were performed in
order to determine their activity, as well as a molecular modeling study to predict the interaction
of the isolated enantiomers with the Tubulin protein. That enantiomers interact differently with
the protein in both the in silico and the in vitro tests. The molecular modeling study was extended
to all intended acridinones to predict a possible interaction with the Tubulin protein. A cell
migration test (Wound Healing) was performed for some of the obtained acridinones, which
determined the inhibition profile of cell migration, a desired characteristic in metastasis cases.

Benthic algae proliferate through the retention of nutrients present in the water. Growing faster in high organic contents water. This uncontrolled proliferation cause an oxygen water concentration decrease, which impacts the fauna of the ecosystem in question, motivating the removal of algae from these sites by the environmental protection agencies, which guarantees the viability of biomass for phytochemical studies, without causing environmental impacts. Marine plants need to produce secondary metabolites related to predators defense, in a critical concentration enough to mitigate the seawater dilution effect. Thus, marine natural products tend to have high biological activity in low concentrations. The perspective of compounds with biological activities of interest to human health justifies the study of marine natural products, especially using tools such as molecular modeling and structural modification, as a way of equating the relation between activity and toxicity, which motivated the accomplishment of this study about of the activity of seaweed extracts against Leishmania infantum and Neobenedenia melleni. The genus Leishmania comprises digenetics protozoa, that live alternately in vertebrate hosts and vectors insects, wich is responsible for the transmission of the parasite from one host to another. L. infantum is one of the species responsible for leishmaniasis visceral occurrence, a clinical form of the disease that affects, in addition to humans, other vertebrates, mainly dogs. Different concentrations of crude extracts and basic fractions of Ulva fasciata, Ulva flexuosa, Dictyota menstrualis and Sargassum vulgare against L. infantum promastigotes were tested, where after the incubation period of 72 hours at 26ºC the reagent resazurin, an indicator of mitochondrial metabolic activity. With the exception of the basic fraction of D. menstrualis, the others extracts and fractions showed no activity against the parasite, at the concentrations tested (0 - 128 μg/mL). The basic fraction of D. menstrualis presented IC50 of 55.08 μg/mL, which shows the potential of natural marine products as a source of bioactive compounds. The bioguided fractionation of the basic fractions of D. menstrualis and H. musciformis originated the HBH and F2' fractions, respectively presenting IC50 values = 30,4 and 62,2 µg/mL, demonstrating the importance of the fractionation steps, for optimization biological activity. N. melleni is an ectoparasite of marine fish, with a marked occurrence in culture systems, responsible for large losses for the mariculture industry. It is mainly fixed in the host's eyes, causing blindness, erratic swimming and difficulty in feeding, which can lead to death if not treated. The main treatment is through freshwater baths, which cause osmotic shock and consequent detachment of the parasite. Due to the logistics and high costs involved in this form of treatment, it is of great interest to develop alternative treatments for the control of this parasite. Given the few studies about its physiology and metabolism, previous studies on the potential pharmacological targets to be explored are necessary. In this context, the main sterols present in the lipid extract prepared from the tissues of the parasite were identified by Bligh & Dyer (1959), and evaluated by TLC and GC-MS. It was found that the parasite presents the precursors squalene and desmosterol, as well as cholesterol and cholesterol esters, indicating that the parasite possesses the enzymatic complex necessary for cholesterol biosynthesis and its storage as esters. In this way, the enzymes involved in cholesterol biosynthesis represent potential pharmacological targets for the control of N. melleni.

Currently, the search for renewable and clean energy resources, important and strongly interconnected characteristics, is gaining increasing prominence in scientific research. Within this focus, great interest has been dedicated to the energy efficiency of a category of oxygenated fuels: polyoxymethylene dimethyl ethers (POMDME). Dimethoxymethane (DMM, CH₃OCH₂OCH₃) is found in this group, offering cleaner combustion, free from soot and polluting oxides such as SOx. This study aims at proposing a sub mechanism of initiation steps for the DMM combustion and pyrolysis kinetic models. Specifically, the kinetics and thermodynamics of DMM unimolecular reactions are discussed. Calculations were performed at the M06-2X/aug-cc-pVTZ level including geometry optimizations, vibrational frequencies and reaction paths calculations. Results suggest that the dissociation reaction pathway, forming CH₃ + OCH₂OCH₃, is the main reaction channel, with the lowest dissociation limit, 82.40 kcal.mol^-1. The reaction channels that lead to H₂COCHOCH₃ + H₂, CH₃O + CH₂OCH₃ and HCOCH₂OCH₃ + H₂ are competitive, with reaction barriers of 85.90, 87.38 and 87.95 kcal.mol^-1, respectively. Hydrogen atom dissociation pathways, with a dissociation limit of 94.56 and 95.86 kcal.mol^-1, and the decomposition reaction that leads to H₂ + CH₂OCH₂ + H₂CO are unfavorable, both from the kinetic and thermodynamic points of view.Changing the focus of the study to the decomposition reactions of the primary radicals, the pathways that lead to HCO + CH₂OCH₃, H₂CO + HCOCH₃, H₂COCHO + CH₃ are highlighted because they are the most favorable, with reaction energies in the respective values 15.87, 9.97 and -1.76 kcal.mol^-1, the latter having an exothermic profile. Results for the dissociation reactions agree with the literature data. The kinetics of decomposition reactions, on the other hand, represent a new contribution to this work. Kinetic parameters, calculated with the canonical variant transition state method, for the most important reaction channels, contributed to the inclusion of these steps in the combustion model for dimethyl ether, as well as the composition of the combustion model for DMM. Finally, the thermodynamic and kinetic information on the unimolecular processes related to the combustion of DMM obtained in this work have shown to be an important contribution to the understanding of the combustion of alternative POMDME fuels.

This work aims to investigate the action of theoretical chemical kinetics models for the treatment of combustion chemistry related problems. Four different cases were studied. In the first case, the hydrogen abstraction reaction channel in the formaldehyde + hydroxyl radicals reaction mechanism was investigated at the CCSD (T) / CBS level, with a pre-barrier complex and a saddle point stabilized by 3.31 and 1.35 kcal mol^-1 with respect to the reactants, respectively. However, Gibbs free energy profile suggests that the formation of the pre-barrier complex at temperatures above 550 K is an endergonic process. Therefore, above this temperature value the reaction can be considered elementary, and the calculation of the rate coefficients is suggested by the canonical variational transition state theory method. In the second case study, the kinetic investigation of the decomposition of formic acid was carried out. Although the two main pathways, decarboxylation and dehydration, presented very similar barrier values, 65.40 and 65.03 kcal mol^-1, respectively, at the CCSD(T)/CBS level, the prevalence of the dehydration pathway can be explained by the isomerization reaction between the Z and E conformers. The rate coefficient for the formation of the Z-conformer is always higher than that for the other conformer. Furthermore, through RRKM calculations and subsequent solution of the master equation, it was found that the transition from the second order regime to the falloff regime occurs at 0.5 atm at 1400 K. In the third case study, five initiation steps in acetone combustion mechanism were investigated: four unimolecular reactions and one bimolecular reaction, the latter being the abstraction of hydrogen by molecular oxygen. These reactions were analyzed at the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ level. Rate coefficients were calculated using the RRKM theory with subsequent solution of the master equation, for the unimolecular reactions and for the bimolecular reaction the canonical transition state theory was applied. The dissociation reaction, breaking of the C-C bond, proved to be the main route among the unimolecular steps. The combustion mechanism proposed by Sarathy was optimized by the insertion of the calculated kinetic parameters calculated for acetone, and the error in the prediction of ignition time was reduced from 81% to 24%. Finally, in the fourth case study, 0D simulations of an ideal Otto cycle were performed with the following fuels: acetone, butanol, ethanol, butanol/ethanol and acetone/butanol/ethanol. A spark model was proposed through the dissociation of 5% of oxygen and fuels. In the integration of the combustion mechanism, the analysis of reaction rates demonstrated that all fuels are mainly initiated by the reaction of oxygen atoms with methyl radicals, generating formaldehyde and hydrogen atoms. These atoms pass through some stages until the formation of hydroxyl radicals, which react with the fuels through hydrogen abstraction reactions. After analyzing the case studies, it is concluded that the choice of the quantum mechanical method combined with thermodynamics, the appropriate kinetic model and numerical analyzes generated satisfactory results, capable of proposing solutions for open discussions in the literature, new rate coefficients and interpretations from a combustion mechanism.

Oxidative stress, resulting from the imbalance between the production and elimination of free radicals, is of great importance in the processes of aging and cell death. The intake of condiment herbs, as salt substitutes, has been stimulated by the fact that they contain bioactive compounds capable of deactivating free radicals. The objective of this work was to determine the content of phenolic compounds and total flavonoids (Folin-Ciocalteu and Aluminum Chloride method, respectively), to evaluate the antioxidant capacity (DPPH and FRAP methods), and to promote a phytochemical screening of the aqueous leaf extract of Petroselinum crispum var. crispum (parsley). Twenty-nine glycosylated flavonoids were identified in the extract, with apiin being the main compound; from the acid hydrolysis of the apiin, the aglycone apigenin (90% purity) was obtained. A high content of phenolics (12.49 ± 1.70 mg GAE / g of parsley extract) and total flavonoids (15.05 ± 2.20 mg of quercetin equivalents / g of parsley extract) were quantified in parsley, in addition to high antioxidant activity (EC50 - 15.50 mg.mL-1, DPPH method) and (189.8 mM Fe (II) / mg of dry plant extract - FRAP method). In vivo tests with Saccharomyces cerevisiae cells showed low toxicity of the aqueous extract of the parsley, however it revealed a high dose-dependent antioxidant potential, mainly in the lipoperoxidation test. In addition, the glycosylated flavonoid apiin also showed antioxidant action on yeast cells under oxidative stress in the cell viability assay (0.1 mM) and lipid peroxidation (0.01 and 0.1 mM), while apigenin was slightly antioxidant. Therefore, it is likely that the antioxidant activity of apiin is related to the total antioxidant capacity of parsley.

Cardiovascular diseases, especially thrombosis, are associated with ischemic heart disease and stroke, which according to the 2010 Global Disease Burden Study have collectively caused one in four deaths worldwide. Essential oils (OE) have great importance in the development of research, for example synergistic effects with oral anticoagulants have already been reported, indicating a possible antithrombotic property. The objective of this work was to evaluate the chemical composition of Schinus molleL essential oil. and to analyze its activity on hemostasis, as well as monoterpene myrtenol. In order to extract the essential oil from the leaves of Schinus molle L., the hydrodestillation technique was used through the Clevenger apparatus, and the material obtained was characterized by CG-DIC-MS. Anticoagulant action was performed by TTPa and TP tests, and the platelet aggregation assays were performed in an aggregometer following the turbidimetric method of Born & Cross (1963), using ADP and collagen as inductors of aggregation. In the chemical characterization of the OE, 45 substances were identified, the major components being sesquiterpenes (88.77%), of which α-Muurolol and δ-cadinene represented 22.85% and 9.66%, respectively, a result confirmed by the comparison of spectra (5mg.ml-1), using ADP as an inducer, showed higher inhibitory power (80%) and the highest concentration (40mg.ml-1) inhibited 48% of platelet activation. Using collagen as an inducer, OE showed no significant activity, as well as showing activity in the coagulation assays, suggesting that the antithrombotic action of OE is especially targeted via platelet aggregation, possibly by the inhibition of P2 family receptors, which are activated by ADP. Mirtenol showed antiplatelet activity using the two inducers and reached 98.5% inhibition of platelet aggregation, and this was a very satisfactory result, and its inhibition of aggregation was more potent in the induction of collagen. In contrast, mirtenol did not interfere with blood coagulation tests, which directs its antithrombotic activity to the antiplatelet action. The OE of S. molle L. presents mainly sesquiterpenes, besides having antithrombotic activity exclusively through inhibition of platelet aggregation, possibly induced by ADP, because OE does not interfere in the blood coagulation pathways and does not act on the induction by collagen. The monoterpene mirtenol has antithrombotic activity exclusively through the antiplatelet route, being its activity pronounced by the induction of the collagen. These results are very useful for following the studies with other inducers of platelet aggregation and future in vivo studies, in order to promote scientific bases for the development of a herbal medicine that can be used in the prevention or treatment of cardiovascular diseases. This is the first report of the antiplatelet action of Schinus molle L. and the monoterpene myrtenol

Multicomponent reactions (MCR) have received great attention in organic synthesis and medicinal chemistry, since they allow the design of new molecules and pharmaceuticals, in special, with great structural complexity and excellent yields. In the Biginelli reaction, the reactants are an aldehyde, a β-ketoester and urea or thiourea leading to a myriad of dihydropyrimidinones/thiones. From the possible combinations of the reactants, three reaction pathways can be expected: the Knoevenagel pathway, the iminium ion pathway and the enamine pathway, being the second pointed out, from both experimental and theoretical works with common aromatic and aliphatic β-ketoesters, as the most probable initiation route. However, if a coumarin β -ketoester derivative is used, the Knovenagel pathway seems to prevail. In order to understand the differences between these reaction pathways, this work has been proposed aiming to the calculations of the possible reaction paths in the coumarin β-ketoester + benzaldehyde + urea MCR and to the understanding of the contribution of the coumarin nucleus in the β-ketoester moiety for the changes in the reaction mechanism. Geometry optimizations have been then performed at the Density Functional Theory (DFT) level, adopting the M06-2X, B3LYP and BHandHLYP fuctionals and the 6-31+G(d,p) basis set. From our calculations, the stationary points with lower relative energies belong to the Knoevenagel reaction path. All reaction pathways are initiated with the formation of an ion-dipole pre-barrier complex, stabilized by 8.76 – 14.84 kcal mol^-1 (relative to the isolated protonated reactants). The calculated barrier height for the reaction between the coumarin β-ketoester and benzaldehyde (which initiates the Knoevenagel channel) is -18.10 kcal mol^-1 (relative to the isolated protonated reactants). For the enamine and iminium ion pathways, barrier heights are 6.21 kcal mol-1 and -16.27 kcal mol-1, respectively (the enamine pathway is initiated from the coumarin β-ketoester and urea reaction and the iminium ion is initiated form the urea and benzaldehyde reaction). Therefore, the barrier height of the first step in the Knoevenagel pathway is ca. 24 and 2 kcal mol^-1 lower than the barrier heights of the first step in the enamine and iminium ion pathways, respectively. The reaction product in the Knoevenagel pathway is also the most stabilized (20.44 kcal mol^-1 below the isolated protonated reactants, while the products in the enamine and iminium ion pathways are located, with respect the isolated reactants, at 5.85 and -25.04 kcal mol^-1, respectively). The second step in all pathways is the dehydration, and barrier heights are 31.12 and 36.13, 28.85 and 31.99 and 32.60 and 36.25 kcal mol^-1 (Knoevenagel, enamine and iminium ion, respectively). The final steps concern the addition of the third reactant, and the intermediates and transition states belonging to the Knoevenagel pathway remain the lowest energy structures. Thus the Knoevenagel pathway is finally attributed as the lowest energy pathway in this complex mechanism for the coumarin β-ketoester + benzaldehyde + urea MCR. The Knoevenagel intermediate has been experimentally detected, and such previous observation can be justified from our theoretical calculations. These results satisfactorily compare to the experimental observations and demonstrate that the coumarin nucleus in the β-ketoester moiety promotes the change of the mechanism initiation from the iminium ion to the Knoevenagel pathway.

The interaction of light with matter is present in several important processes of nature. Photons are employed by natural systems as energy donors or as information elements. And from the energy from the photons the Z-E isomerization of the C = C bond can be induced as, for example, in the butadiene molecule. Isomerization consists of a photochemical process widely explored and forms the fundamental step in many photobiological processes such as vision, light-induced ion bomb and phototaxis. The project aims to obtain stationary points from the surface of the potential energy for the butadiene molecules substituted with the Cl group, carbonyl substituted butadiene (CHO), butadiene substituted with the amine group (NH2) and butadiene. The surface description generate a model for the understanding of the influence of the groups on the geometry and the process of photoisomerization. As a starting point for the investigations in the excited state, the configurations of the molecules corresponding to the minimum energy states in the ground state were mapped by the Hartree Fock (HF) method. All the molecules were optimized (S0) in the CASSCF method, in which we chose, for the carbonyl substituted butadiene molecules, six orbitals and six electrons, for the chlorinated substituted butadienes four orbitals and four electrons were chosen, for the butadiene substituted with amine and butadiene two orbitals and two electrons were chosen. In addition to the minimum in the excited state, we found some minimums at the conic intersection (IC) for Chloro-butadiene, others for butadiene, three minimums for IC for pentadienal and still others for the amine-butadiene molecule. When comparing the results of the IC minimums with the results found in the literature it is realized that the substituents do not significantly alter the geometry of the intersection of the butadiene without substituent. An IC was also found that is possibly associated with the chlorine dissociation process, however, no other CI was found similar to it in the literature. This possible dissociation may be a third path of reaction, the other two pathways being isomerization and electrocyclization.

Propolis is a resinous natural products elaborated by honeybees from different parts of plants, such as shoots and flowers. Its chemical composition is very complex and depends on factors such as climate, seasonality, soil, vegetation and also the bee species. Propolis has currently been identified as na importante source of bioactive compounds due to its high biological potential, with anti-inflammatory, antibacterial, antitumoral, antiparasitic and antioxidant activities. In this work, ethanolic and n-hexanic extracts were prepared from three samples of green propolis obtained in different regions of Rio de Janeiro. The quality of these extracts were evaluated using colorimetric methods for the determination of the total phenolic content – total phenolic and flavonoid contents – and also the antioxidant capacity was evaluated by capturing organic free radicals (DPPH and ABTS), as well as the ferric reducing antioxidant power (FRAP). The qualitative chemical profile of the extracts was evalutated through CLAE-DAD analisys, and the influence of the solvente polarity on the extraction profile was studied. The bioactive compounds 3,5-diprenyl-4-hydroxycinamic acid (Artepillin C), 3-prenyl-4-[(3-phenylpropanoil)-oxy]-cinnamic acid (Baccharin) and 2,2-dimethyl-8-prenylcroman-5-propenoic acid were isolated from the n-hexane exrtract by two chromatographic steps: fracionation of crude extract using the mixture of solventes chloroform/acetone in increasing gradiente concentration, followed by purification of fractions of interest by HPLC-UV in semipreparative scale, using the mixture methanol/water in increasing gradiente concentration. All the isolated constituents were characterized by NMR (1H and 13C), UV spectra and CG-MS techniques, and the contente of these componentes in the crude extract was quantified through HPLC-DAD in reverse phase. The antiparasitic activity of green propolis and its active principles was evaluated against amastihote and tripomastigoe forms of Trypanosoma cruzi, the parasite responsible for causing Chagas’ disease. 

Monoamine oxidase [EC 1.4.3.4 (MAO)] is an enzyme located in the outer membrane of the mitochondria, which uses flavin adenine dinucleotide (FAD) as a cofactor to catalyze the oxidant conversion of an amine in its corresponding aldehyde, also producing ammonia and hydrogen peroxide. MAO activity regulates the levels of biogenic amines present in tissues, especially in the brain. MAO exists as two proteins: MAO-A and MAO-B. These isoforms were defined primarily by substrate affinities and inhibitor sensitivity. Accordingly, MAO-A oxidizes, preferably, serotonin, melatonin, noradrenaline and adrenaline. MAO-B preferably oxidizes phenylethylamine, an alkaloid from the metabolism of phenylalanine. The ingestion of phenylethylamine promotes the release of dopamine that acts in the brain stimulating euphoria. Concerning the inhibitors, MAO-A is preferentially inhibited by clorgiline. MAO-B is inhibited by deprenyl and pargyline. These inhibitorscan be used in the treatment of degenerative brain diseases.Since studies have shown that molecules derived from coumarins achieved excellent results as inhibitors of these enzymes, several new drugs derived from coumarin have been synthesized, which a few are very promising in the treatment of Alzheimer's and Parkinson's diseases. This study aimed to promote in vitro inhibition tests of MAO with new substances derived from coumarin.

The quality standards for biodiesel commercialized in Brazil are set by the National Agency of Petroleum, Natural Gas and Biofuel (ANP), through Brazilian Resolution N^o. 45 of 2014 (RANP 45/2014). RANP 45/2014 sets the maximum free glycerol content in biodiesel added to diesel oil at 0.02% w/w. The higher concentrations of free glycerol could to lead problems in fuel storage tanks, formation of deposits and clogging in the engine injection system and emission of toxic aldehydes. In this work, a new approach to determine free glycerol in biodiesel from  soybean, palm, macauba (pulp) and used frying oils was developed employing the glycerol oxidation by the periodate and, after, masking of the excess periodate by the molybdate. This provided a decrease in the analysis time probably due to excess periodate employed and the determination of iodate formed. The iodate was quantified by the addition of iodide, forming the tri-iodide anion. The iodometric determination was performed in three days with two distinct methods based on the spectrophotometric and titrimetric techniques. In the spectrophotometric method, the glycerol was extracted by partition in ethanol-water/n-heptane and the tri-iodide was determined in the presence of starch (λ = 582 nm). Two analytical curves were constructed after analysis of glycerol standards in a dual and single beam spectrophotometer. The latter had lower precision in the measurements, and its analytical curve presented low limits of detection (1.9 mg L^-1) and quantification (5.7 mg L^-1), and good coefficient of determination (R² = 0.9972). The repeatability of spectrophotometric method was satisfactory (CV < 12%), however the intermediate precision was unfavorable (CV < 39%). The analysis of glycerol standards in water by titrimetric method presented excellent accuracy, with relative errors below 3.0%. Detection and quantification limits were 1.2 mg L^-1 and 3.5 mg L^-1, respectively. Biodiesels were analyzed by titrimetric method after glycerol extraction by partition in water/n-heptane and, subsequent, determination of tri-iodide by the titration with Na₂S₂O₃ standard solution, in the presence of starch. The precision of this method was good in repeatability (CV < 14%) and intermediate precision (CV < 8%). The accuracy of the titrimetric method was evaluated by recovery tests at three fortification levels: 250, 500 and 1000 mg L^-1, reaching 91% to 105% of recovery. The similarity between the glycerol contents obtained in each method, between days were evaluated by ANOVA. The average global levels of free glycerol levels in the biodiesels obtained by both methods did not differ significantly at the 95% confidence level. The overall mean glycerol levels obtained by both methods were similar in the analysis of the biodiesels used in this study, according to the Student's t-test. However, the titrimetric method presented smaller variations between days, lower cost and greater simplicity compared to the spectrophotometric method. In addition, the assay was fast (10 min) when compared to the other analysis techniques described in the literature and of high detection capacity compared to other titrimetric methods.

Sunflower is highlighted in the food industry as a result of its high grain productivity and oil quality. Its properties have been generating special interest on chemical research because of secondary metabolites with biological potential. A limiting factor to be considered for sunflower characteristics is nutrient availability. Among essential micronutrients, sunflower’s culture has high sensibility to excessive input of Boron element (B). This element acts on physiological and morphological processes and, therefore, it affects chemical and agronomic aspects. This work aims to evaluate sunflower’s grain productivity, content and quality of the seed oil. Moreover, the biological potential of sunflower’s tissue extracts grown under differential boron supply. During field experiments, three sunflower’s genotypes (Helio251, BRS323 and BRS324) were supplied with different doses of B: 0, 2.5, 5 and 8 kg ha^-1. The B sensibility was evaluated using the amount of grains, content and quality of the seed oil, and B content in grains. The biological potential was determined using the highest B-sensitive genotype (Helio251). Aqueous (0.1 and 0.5%) and ethanolic (0.025 and 0.050%) extracts were produced using leaf and capitulum tissues, which were collected during R5 field stage. Afterwards, “in vitro” and “in vivo”assays led us to estimate antioxidant capacity and activity, respectively. Furthermore, aqueous extracts of leaf and capitulum (2.5, 5 and 10%) were evaluated in relation to its allelophatic potential on seed germination of Digitaria insularis. As a result, genotypes shown distinct response for B fertilization on field experiment. This micronutrient influenced grain productivity of the Helio251 and BRS323, and oil content in all genotypes. However, B was not recognized on major unsatured fatty acid profiles and grain protein. Despite of that, it was observed genotypical differences in oil quality, either on fatty acid parameters or on crude protein content. In vitro evaluation of hydroalcoholic and aqueous extracts of leaves and capitulum confirmed phenolic content, absence of flavonoids and antioxidant capacity, with ABTS and FRAP methods. As to the Saccharomyces Cerevisiae biological model shown antioxidant activity in aqueous and ethanolic extracts using “in vivo” assays. However, better values for antioxidant activity were found using ethanol as extraction solvent. Through analysis of HPLC, it was confirmed chlorogenic antioxidant compounds. This work allowed us to observe multiple functions of B, and its biological potential in sunflower leaves and capitulum extracts. It was noticed that B element influences sunflower crop production either negatively or positively, depending on the applied dose and genotype. In summary, the amount of antioxidant components changes with B supply. Moreover, sunflower has secondary metabolites with allelopathic and antioxidant contents that have potential to be useful for both chemical and agricultural industries.

Alzheimer's Disease (DA) is one of the most common dementias in individuals over 65 years of age. It is a progressive illness that affects the thought, memory, learning and language leading the elderly to dependence on their relatives due to the inability to perform activities in their everyday life. One of the main pathological mechanisms responsible for DA is the intense synaptic degeneration where the neurotransmitter acetylcholine (ACh) suffers hydrolysis in presence of cholinesterase’s enzymes, in particular acetylcholinesterase (AChE). Maintaining the proper functioning of synapses in the central and peripheral nervous system is related to inhibition of these enzymes. Previous researches showed compounds derived from Pyrazoline or Sulfonamide as promising enzyme inhibitors. Therefore, this project aims to hybridize the groups Pyrazoline and Sulfonamide in 20 unpublished compounds for subsequent evaluation of the inhibition capacity of the enzymes AChE and BuChE, involved in synaptic degeneration.

Studies by UV/Vis absorption spectroscopy, fluorescence emission and 77K phosphorescence emission indicated that the dimethoxylated xanthones 1,2-dimethoxy-9H-xanthen-9-one (1,2MX), 2,3-dimethoxy- 9H-xanthen-9-one (2,3MX) and 3,4-dimethoxy-9H-xanthen-9-one (3,4MX) present triplet excited state with a pp* configuration. Studies by laser flash photolysis (l_exc=355 nm) were performed to investigate the reactivity of the triplet excited state of the dimethoxylated xanthones 1,2MX, 2,3MX and 3,4MX toward different types of quenchers. Quenching of 1,2MX, 2,3MX and 3,4MX by 1-methylnaphthalene and 1,3-cyclohexadiene, in acetonitrile, results in the formation of the corresponding triplet excited states through a triplet-triplet energy transfer process controlled by diffusion. The hydrogen transfer reaction of these dimethoxylated xanthones employing alcohols (methanol, ethanol, and 2-propanol) and 1,4-cyclohexadiene occurs through the pure mechanism, with rate constants consistent with the involvement of a triplet excited state with pp* character, confirming the experimental results of the phosphorescence studies. In all cases, the formation of the corresponding ketyl radicals was observed. Using the electron donors DABCO and triethylamine as quenchers of the triplet excited state of 1,2MX, 2,3MX and 3,4MX the formation of the corresponding radical anion by electron transfer was observed. On the other hand, quenching with phenol and its derivatives led to the formation of the ketyl/phenoxyl radical pair, while using indole or the methyl ester of N-acetyl tryptophan (NATME) the ketyl/indolyl radical pair was formed. In all cases, the reaction takes place through a mechanism involving an electron transfer coupled to an ultra-fast proton transfer. Comparing the quenching rate constants for the dimethoxylated xanthones1,2MX, 2,3MX and 3,4MX, it can be concluded that there is no relevant difference between their reactivities. Photolysis of 2,3MX in H₂O/acetonitrile solution (1:1 v/v) (l_exc=266 nm) resulted in its photoionization with the formation of the corresponding radical cation (l_max~390 nm). The characterization of this radical cation through the use of the nucleophilic quenchers chloride, bromide and acetate leads to quenching rate constants with diffusion-controlled values. Finally, 1,2MX, 2,3MX and 3,4MX were used as photosensitizers for singlet oxygen formation, although presenting very low efficiency (F D¹O₂: 1,2MX = 0.19; 2,3MX = 0.12 and 3,4MX = 0.06).

Cancer and bacterial infections are diseases that cause a large number of deaths, and despite the existing treatments, drugs being less harmful to the patients and more active against resistant cells are still needed. Coumarin derivatives and several classes of Ru(II) complexes have been studied for their potential as antimicrobial and antitumor agents. For this reason, four novel coumarin-N-acylhydrazone hybrid ligands of the type (E)-7-(diethylamino)-N'-(4-R-benzylidene)-2-oxo-2H-chromene-3-carbohydrazide (HL2: R=H; HL3: R=Cl, HL4: R=Br, HL5: R= OCH₃), were obtained from condensation reactions, using one hydrazide (7-(diethylamine)-2-oxo-2H-chromone-3-carbohydrazide, HL1) and different p-substituted aldehydes. Reactions between HL2-5 and cis-[RuCl₂(DMSO)₄] afforded the complexes trans-Cl-[RuCl₂(DMSO)₂(HLn)], C2-5 (Ru(II)-Cl-DMSO class). Concomitantly, hydrolysis of the ligand occurred, resulting in the formation of the complex trans-Cl-[RuCl₂(DMSO)₂(HL1)] C1, containing the hydrazide as ligand. Crystal structures of HL2, HL3 and the complexes C2-5 were determined by single crystal X-ray diffraction, that revealed E/Z isomerization of the coumarin-N-acylhydrazones upon coordination, where the free ligands were found in the E form, and when complexed, the Z isomer was formed. Complexes C2-5 exhibited the Ru(II) atom in a distorted octahedral geometry, where the coumarin ligand is coordinated in the keto form through the hydrazone carbonyl and the iminic nitrogen. Attempting to synthesize a second class of complexes, containing bipyridine as auxiliary ligand and charged, ([Ru(bipy)₂(HLn)]PF₆ - Ru(II)-bipy class), the reaction between HL2 and cis-[Ru(bipy)Cl₂] was carried out. However, the possible hydrolysis of the ligand precluded the isolation of the desired complex. A similar methodology using cumarin-b-ketoester hybrids HL6-8 yielded the complexes from the Ru(II)-bipy class, [Ru(bipy)₂(HLn)].PF₆ C6-8. The XRD analysis of C7 shows the Ru(II) ion in a distorted octahedral environment with the ligand coordinated through the deprotonated b-ketoester portion and two bypiridines in the coordination sphere. Antiproliferative evaluation of the compounds against the tumor cell lines (4T1: murine mammary carcinoma and B16-F10: murine melanoma melanoma) and non-tumor (BHK-21: hamster kidney) showed that overall, the coumarin-N-acylhydrazone and coumarin-hydrazyde hybrids HL1-5 were more active than the complexes C1-5, where the IC₅₀ values for the ligands were found in the range of 10.6 to 50. 4 mM and between 17.7, and 97.8 mM for the complexes. On the other hand, the coumarin-b-ketoester ligands HL6-8 were inactive (IC₅₀ > 100 mM), yet the complexes C6-8 presented high cytotoxicity, with IC₅₀ values ranging from 2.0 and 12.8 mM. For the antimicrobial assays, HL1 was the only ligand active against one gram-negative bacteria strain, however its MIC was not determined within the studied concentrations. Among the complexes, all demonstrated activity only against gram-positive bacteria strains. Within the Ru(II)-Cl-DMSO complexes, only C3 and C4 (R = Cl and Br) exhibited MIC under the concentrations used (40.5 and 86 μM). On the other hand, the complexes from the Ru(II)-bipy class C6-8 presented MIC between  2.20 and 9.22 μM. Comparing the classes of complexes, Ru(II)-bipy and Ru(II)-DMSO, the greater activities presented by the former in both biological studies was attributed to the presence of charge and of bipyridine ligands. The investigation of DNA interaction of the complexes [Ru(bipy)₂(HLn)]PF₆ (C6-8) are in progress.

One hundred and fifty samples were analyzed for suspected cocaine content. The samples were seized by Polícia Civil do Estado do Rio de Janeiro from the year 2016 to 2017 on the city of Rio de Janeiro, Baixada Fluminense and Costa Verde, and 102 samples showed powder aspect and 13 samples showed crack aspect. The samples were analyzed for cocaine and adulterant contents and for the identification of diluents. The main objective of this work was to evaluate the chemical profile of cocaine (powder and crack), as well as to compare different analysis techniques. The importance of the identification and quantification of cocaine adulterants relies on their pharmacological properties, adverse effects and synergistic activities with cocaine, possibly increasing the duration of the effects, its intensity and toxicity. Preliminary tests (Scott test, Wagner test, AgNO₃ precipitation, iodine / iodide test and acid hydrolysis) were initially conducted to verify the possible presence of cocaine. Cocaine and adulterants were identified and quantified by Gas Chromatography Coupled to Mass Spectroscopy (GC-MS), using commercial standards of caffeine, lidocaine, phenacetin and benzocaine. The cocaine pattern was obtained by purification (> 98%) and was ceded by Prof. DSc. Bruno Sabino (UFRJ / PCERJ). Other adulterants eventually found were identified by Mass Spectrometry with the aid of a commercial library. The detection of diluents (inorganic substances and sugars that are frequently added to cocaine in order to increase yield) was performed by Raman Spectroscopy and Infrared Spectroscopy (FT-IR), using the following commercial standards: calcium carbonate (CaCO₃), sodium bicarbonate (NaHCO₃), aluminum sulphate (Al₂(SO₄)₃), sodium carbonate (Na₂CO₃), starch, sucrose, glucose, lactose and mannitol. The capacity to detect cocaine and adulterants by Raman and FT-IR spectroscopy were also evaluated, according to previous quantification performed by GC-MS. It was verified the efficiency of the preliminary tests, the differences between crack and cocaine chemical profiles and possible differences among the three main criminal gangs of the state of Rio de Janeiro. Cocaine was not identified in only two powder samples. It was observed higher cocaine contents in crack samples, showing an average of 29.77 ± 14.54% of cocaine, compared to an average of 7.31 ± 3.39% in powder samples. The most frequent adulterant identified in powder samples was caffeine, that was present in 93% of the samples, while crack samples were majorly adulterated with phenacetin, that was present in 92% of the samples. Calcium carbonate, sodium bicarbonate and starch were the diluents most frequently found in powder samples, which could be identified by associating the two spectroscopic technics (Raman and FT-IR). It could be observed, by statistical analysis, similarities according to the type of the samples (hydrochloride and freebase) as well as significant differences among certain criminal gangs.

Canine Cognitive Dysfunction (CCD) is a neurodegenerative disorder that affects older dogs and is very similar to Alzheimer's Disease (AD) in humans. Both pathologies are considered multifactorial and present evidence of b-amyloid deposition; oxidative stress; hyperphosphorylation of Tau protein; imbalance in neurotransmitter levels, such as acetylcholine (ACh); among other factors. Since ACh plays a key role in cognitive processes and many AD treatments are based on the use of acetylcholinesterase inhibitors (AChE), this work aimed to evaluate the efficacy of teas, phytochemicals and synthetic compounds in the in vitro inhibition of this enzyme in dogs brain. This first part of the paper composes chapter 1 of this thesis. The tea of Peumus boldus presented prominence in this study proving effective in the inhibition of this enzyme and with significant antioxidant potential. The phytochemical quercetin and synthetic compounds Cum3 and Cum4 have stood out as competitive inhibitors of AChE activity. The effect of these compounds, as well as of boldo tea, on the serum activity of butyrylcholinesterase (BChE) in dogs was also evaluated. However, all treatments were more effective in inhibiting brain AChE activity than BChE activity in serum. In order to evaluate the effect of CCD on blood enzymes in dogs, blood samples from 48 dogs divided into 5 groups were evaluated: control, risk group, mild DCC, moderate DCC, severe DCC. This part of the paper composes chapter 2 of this thesis. The enzymes evaluated were cholinesterases (using as substrate acetylthiocholine or butyrylthiocholine) and two enzymes of the antioxidant system: catalase and glutathione S-transferase. Although there was no significant difference between the activities of these enzymes in the five groups studied, it was possible to observe changes in the average activities of cholinesterases (using acetylthiocholine as substrate), catalase and GST. These differences show that although such enzymes are not shown to be suitable as CCD biomarkers, they may in future be used as adjuvants in the analysis of disease evolution and in the assessment of response to treatment used. The results obtained in this study, although still early, are promising and may contribute to an advance in the studies of new forms of diagnosis and treatment of CCD.

The chromatographic techniques applied to Uroclhoa ruziziensis extracts and partitions, together with the application of physical methods of organic analysis, allowed the isolation and identification of eight substances, among them the organic acids already known in the genus, one flavonoid, tricin, and two steroidal saponins, dioscin and collettinside III, and the triterpene saponins 3-O-β-D-glycopyranosyl sitosterol and 3-O-β-D-glycopyranosyl stigmasterol. In addition to the classical phytochemical study the crude extracts of U. ruziziensis and U. humidicola were analyzed by dereplication using UPLC-MS (Ultra Performance Liquid Cromatography). Their profiles were compared, being common the presence of diosgenin and penogenin skeleton saponins, together the sugar type unities rhamnose and glucose. In the species U. ruziziensis it was possible to identify seven more substances, among them four flavonoids, carinoside, schaftoside, isoschaftoside and ombuin 3-O-rutinoside. The saponin dioscin and / or collettinside III, that were also identified during chromatographic isolation and protodioscin and penogenin 3β- O- β-D-glucopyranosyl-[(2-1)-O-α-L-rhamnopyranosyl-(4- 1)-O-α-L-rhamnopyranosyl. In U. humidicola it was possible to identify, through dereplication, five substances. Tricetin derived flavonoid, tricetin 7-methyl-ether-3’-O-β-D-glucosyl-5’-O-α-L-rhamnoside and the suggestion of unprecedented tricetin 4’-O-β-D-glucosyl-[(2-1)-α-rhamnosyl-(4-1)-α-L-rhamnopyranosil]. The saponins Pariphyllin A, Solanigroside H and 3-O-β-D-glucopyranosyl-(1-4)-α-L-rhamnopyranosyl-(1-4)-β-D-glucopyranosyl-(1-4)-[α-L-rhamnopyranosyl- (1-2)]-β-D-glucopyranosyl spirost-5-eno. Specific differences were noticed mainly in the flavonoid types presente in both, since in relation to the metabolite classes we expected the identification of steroidal saponins and flavonoids.

The contribution to the phytochemical study with the species Cespedesia spathulata, allowed expanding the knowledge regarding the phytochemical composition of the species. In addition to the ochnaflavone biflavonoid already identified, chromatographic processes and physical analysis methods allowed to the identification of additional twenty six substances. The ethyl acetate partition, derived from the raw leaf extract of this species, and the ochnaflavone, catechin and epicatechin mixture, isolated from the same partition, had their enzymatic influencing potential tested against the action of the tyrosinase enzyme. Both partition and catechins showed activation on the action of the enzyme, 104% and 384%, respectively.

In this work it was synthesized novel cobalt complexes containing a fluorescent hybrid ligand of coumarin-b-ketoester (HL) of the type [Co(L)(Am)](ClO₄)_n, where L is a coumarin derivative in its anionic form and Am is the auxiliary amine: TPA (for 1b-Co^II and 2b-Co^III) or Py₂en (for 2c-Co^III). The synthetic procedure to obtain 1b led to the formation of the Co^II specie (1b-Co^II), which was confirmed by CHN elemental analysis, molar conductivity and X-ray diffraction (XRD). The 1b-Co^II ion complex is a cationic hexacoordinated specie, containing the coumarin in the L^1- form, acting as O,O-donor, and a neutral TPA as N,N',N',N'-donor. XRD results obtained for HL and 1b-Co^II showed that the complexation led to the increase of ligand planarity. For 2b-Co^III, the use of [Co^III(TPA)Cl₂]ClO₄ as a starting material led to the formation of the Co^III complex, however, CHN elemental analysis and ¹H NMR also indicated the presence of the precursors in the isolated solid. The complex 2c-Co^III was obtained from the same methodology used for 1b-Co^II, however, the presence of a more basic amine (Py₂en) favored the Co^III specie. Elemental analysis, molar conductivity, infrared and ¹H NMR spectroscopy data indicated a structure of the type [Co^III(L)(Py₂en)](ClO₄)₂, where L^1- also interacts with the metal through the carbonyl groups of the b-ketoester moiety. DFT calculations showed that the band at 448 nm in the UV-Vis spectra of 1b-Co^II, obtained in buffer solution (pH 7,4), refers to the p-p* transition centered on L^1-, and for 2c-Co^III the band at 455 nm is related to a mixture of p-p* and LMCT transitions. Cyclic voltammetry showed that the complexes exhibit a quasi-reversible process associated with the Co^III/Co^II pair, with E_pc in the order 2c-Co^III < 1b-Co^II < 2b-Co^III, which was associated to the electronic properties of the auxiliary amine. The higher p-acceptor character of the TPA facilitates the electron gain by the cobalt in 1b-Co^II and 2b-Co^III, while Py₂en, which has a larger s-donor character, leads to a lower potential for 2c-Co^III. HL exhibits a cathodic process associated to the reduction of the carbonyl groups, which did not shift after coordination. Reactivity assays of 2c-Co^III in buffer solution (pH 7,4) monitored by fluorescence spectroscopy indicated that the ligand was released in the presence of a reducing agent (sodium ascorbate) for 8.5 h, which was most pronounced in argon atmosphere, suggesting that dissociation of L^1- occurs preferentially after reduction of the metal. 2c-Co^III was stable in buffer solution without reducing agent. The cytotoxicity investigation of HL, 1b-Co^II and 2c-Co^III against B16-F10 (metastatic murine melanoma), 4T1 (murine mammary melanoma) and BHK-21 (non-tumor cell of hamster kidney) showed that the free ligand was not active, but the coordination favored its cytotoxicity in most cases. 2c-Co^III exhibited the best overall activity when compared to 1b-Co^II, presenting selective cytotoxicity to cancer cells (45.9 ± 5.2 mM e 39.1 ± 6.6 mM para B16-F10 e 4T1, respectively) and being inactive against normal cells (71.2 ± 6.2 mM).

Fipronil (FIP) is an insecticide belonging to the class of phenylpirazoles. It is widely used as an insecticide in agriculture and in veterinary medicine. Its mechanism of action is involved with blocking the signal transmission due to the γ-aminobutyric receptor antagonism (GABA) present in acari and insects. Increased human-pet interaction makes concern for the prevention and treatment of flea and tick infestations. The products commercially available for ectoparasites treatment in dogs and cats are mostly in the topical form, however they are associated with damage to the animal, owner and to the environment, due to uncontrolled exposure to the drug, leading to requirement of new product development. Pharmaceutical forms for oral administration of drugs are most common used for the convenience they provide, constituting a non-invasive route of administration and having a low cost. The objective of the study was the pharmacotechnical design and physical-chemical quality control of immediate release tablets of fipronil, as well as to determine its pharmacokinetics and the ectoparasiticide efficacy in dogs. The results showed that it was possible to produce FIP tablets according the criteria established in the Brazilian pharmacopoeia. In vitro release studies have shown that the best diluent to be used in tablet development is lactose due to the appropriate release profile for immediate release tablets. FIP administered orally at the dose of 2 mg / kg reached the systemic circulation (Cmax = 2.17 μg / mL) and was fast absorbed (tmax = 2.67 h) and metabolized, once its SULF metabolite presented Cmax = 1.32 μg / mL in a tmax = 3.5 h. Both elimination, FIP and SULF occurred slowly (t1 / 2 = 385.93 h) and (t1 / 2 = 385.93 h) respectively, maintaining quantifiable plasma levels in the blood for up to 28 days after treatment. The in vivo ectoparasiticide efficacy tests proved that FIP administered orally at the dose of 2 mg / kg had a efficacy of 80% against C. felis felis for 15 days after treatment but it did not show any efficacy against R. sanguineus.

Doxycycline is an antimicrobial agent from the tetracycline family that acts inhibiting the synthesis of bacterial proteins by binding, principally, to the 30S subunits of bacterial ribosomes, preventing the access of the aminoacetyl-tRNA to the receptor site in the mRNA-ribosome complex. It is often the choice for the treatment of canine Ehrlichiosis. Currently, doxycycline is available in the veterinary market under the pharmaceutical forms: tablet and suspension. It is a class well studied, in the literature are easily found articles describing the methods of analysis for determination of the components of this class in human plasma, however, in canine plasma the methods described by HPLC-UV are scarce, having microbiological methods being more used. In this work, a method was developed and validated for the determination of doxycycline in canine plasma. The samples were submitted to liquid-liquid extraction with low temperature partitioning (LLE/LTP) followed by separation by reverse phase liquid chromatography (RP-LC), using as the mobile phase acetonitrile / water adjusted to 2.5 with oxalic acid (80:20 v/v), the gradient flow between 0.8-1.0 mL/min, with ultraviolet (UV) detection at 357 nm. Oxytetracycline was used as internal standard (IS). The validation of the method showed selectivity, sensitivity, absence of matrix and residual effects, and stability. The linearity of the method was established in the range of 0.5-10 μg/mL (r > 0.99), with lower limit of quantification (LLOQ) in 0.5 μg/mL. Intra- and inter-day accuracy presented CV values of less than 20% for LLOQ and 15% for other quality control samples and intra and inter-day accuracy values expressed in RSE, presented in the range of ±20% for LLOQ and ±15% for the other quality control samples. The method was fully validated, taking into account all the parameters of ANVISA's legislation. The methodology was applied for analysis of comparative pharmacokinetics of doxycycline administered orally from two solid dosage forms: chewable tablet and commercial tablet (Doxifin^®). Administration of these formulations reached, respectively, blood circulation (C_max = 1.11 and 1.16 μg/mL), being absorbed (t_max of 240 and 195 minutes) and eliminated (t_½ = 1106.24 ± 130.41 and 1685.919 ± 726.44 minutes) rapidly. The similarity in the plasma profiles of the two formulations tested was observed and bioequivalence was confirmed by statistical tests.

Alzheimer disease (AD) is a common neurodegenerative disease and is considered the most common form of dementia.  According to ONU, due to increase in life expectancy of the world population, the number of people with dementia will grow, achieving 82 million in 2030 and 152 million in 2050. Therefore, AD is considered an important public health problem.

Between the main pathological mechanisms involved in the characteristics lesions of DA studied are protein TAU hiperfosforilation, Ab aggregation, neurovascular disfunction, inflammatory process, oxidative stress, cellular cycle alterations and mitochondrial disfunction. The knowledge of these disturbances has lead to development of drugs with symptomatic effects, approved in many countries, but these drugs act only on the behavioral state, however, advances in the research of pathogenic of AD also has lead to potential disease modifying agents in clinical trials.

Another approach with pharmacokinetic/dynamic and exams of molecular image give rise to the theranostics. This approach of treatment for AD includes therapeutic properties and diagnosis, in only one prototype, with the aim of optimizing the efficacy of drug therapy. In this context of compounds which can act as diagnosis sensor, coumarins show to be an excellent prototype of theranostic agents due to luminescence properties and the large number of pharmacological activities.

Coumarins are natural products widely found in nature and which has an important effect in plants physiology. In the literature, there are many examples of coumarins used for treat AD and as optical sensors of metals applied in biological medium.   

The objective of this work comprises the planning of hybrids coumarins fluorescents which can act as theranostic for AD. Two coumarin series were synthesized and fully characterized. The first series of compounds (CCM) was synthesized by two different protocols of synthesis. Five compounds were selected (59b-e,i) and its photophysical characterization in methanol and water was evaluated. Additionally, the compounds 59a-b showed the ability to act as Zn²⁺ probe in these same solvents.

The second series (HM) was synthesized in four steps, and the compounds 60a-b and 59a-b showed excellent values of inhibitory activities against AChE (12,94nM-128,28nM), very similar to drug Donezepil (6,55nM). The hybrid 60a was still evaluated for the capacity to binding Zn²⁺ in water (pH = 7,4), validating the propose of this work to produce hybrids which can act as theranostic for AD.  

The present work refers to the synthesis of novel dialkylphosphorylacylhydrazones that occurs in 3 reaction steps: the first step consisted in the synthesis of different dialkyl acetate phosphonoacetates obtained by the reaction of the ethylbromoacetate with the trialkyl phosphite of interest. The second step was the synthesis of acetic diethoxyphosphonylhydrazides which occured by reaction between dialkyl phosphonoacetates synthesized and hydrazine. The third and final ones occured by the condensation of acetic diethoxyphosphonylhydrazides with different heterocyclic aldehydes. The obtained compounds were characterized by 1-H and 13-C and 31-P NMR, infrared (IR) and mass spectroscopy (MS). In total, 17 unpublished compounds, namely one to 17, respectively, were obtained with diastereoisomeric mixture of preferential conformation E. The fungicidal activity of each synthesized molecule was tested against plant pathogens fungi responsible for postharvest diseases of economic importance such as Pilidium sp., Alternaria sp., Penicilium sp. and Colletotrichum gloeosporioides, however, they did not present fungicidal activity in the evaluated fungi. The compounds were further tested on melanoma cells, for the purpose of verify whether they have any activity in tumor growth of melanoma cells, but only compounds 2 and 10 showed some biological activity, although relatively low.After synthesis and purification of the synthesized compounds, they are checked against the acetylcholinesterase enzyme activity. The AChE enzyme inhibition assay has shown that compound 2 does not inhibit the enzyme along with compounds 3, 7, 8 and 16 while compound 13 in addition to compound 9 strongly inhibits AChE and even more inhibitors than the standard used, the Propoxur.

The catalytic properties of niobium oxide (V) (Nb2O5-CBMM) of different degrees: amorphous, optical and ultra-pure, untreated or heat treated at 400, 500, 700 and 900 ° C were studied, before and after the interaction with hydrogen peroxide (H2O2), by UV-Visible spectroscopy in diffuse reflectance mode, Raman and FTIR-ATR. The presence of different reaction sites for the NbO7 and NbO8 type systems, which are directly related to the surface defects present in different states of crystallization, was totally characterized. The reactivity of different catalysts obtained from the niobium oxide (V) was investigated using methyl linoleate oxidation in the presence of H2O2 as a probe reaction. The reaction was monitored by GC-MS, as well as by 1 H and 13 C NMR spectrometry, with the dominant product of the reaction being 9-oxo-nonanoic acid methyl ester. Based on these results, a reaction mechanism was proposed involving an auto-oxidation process that initially leads to the formation of hydroperoxides that decompose rapidly via a Hock-like rearrangement, leading to the formation of aldehydes.

Brazil has the greatest bíodíversity in the world, but it needs to value and promote knowledge
of local biodiversity. The species M. multiflora (lam) DC., popularly known as "pedra-ume-caá"
(purple fruit), is a native species that belongs to the Myrtaceae family and occurs in Brazil from
the north to Rio Grande do Sul. The species Psychotria leiocarpa Chamo & Schltdl., popularly
known as "cafeeiro do mato" (blue fruit), is a native species that belongs to the Rubiaceae family
and occurs from Paraíba to Rio Grande do Sul. The characteristic coloration of the fruits (purple
and blue, respectively) of both species draws attention to its potential for use as a natural
colorant. The seasonality in which fruiting occurs has generated difficulty in the phytochemical
characterization of fruits of plant species. In this context, the two species remain without
investígation of the special (secondary) metabolites produced in the fruits. Thus, the aim of this
work was to characterize the fruits of M. multiflora and P. leiocarpa. The quantification of
anthocyanins, carotenoids and phenolic acids present in the fruits of M. multiflora was
performed by HPlC-DAD and the antioxidant capacity was evaluated by free radical capture
methods (DPPH and ABTS). The f1avonols present in fruits of this species were isolated by
accelerated liquid chromatography in reversed-phase column. The methanolic extract of P.
leiocarpa fruits was subjected to partítion in chloroform: water, the aqueous fraction was
subjected to HPLC separation on a reverse phase analytical column coupled to the channel
selector valve and the chloroform fraction was subjected to classic chromatography on a normal
phase column. The isolated substances of both species had their structures determined through
the interpretation ofthe spectral data furnished by UV, 1D and 2D NMR and high-resolution MS
(HRMS) involving comparison with data in the literature. Twenty-one substances were identified
for the first time in the fruits of M. multiflora, among which carotenoids, flavonoids and phenolic
acids were characterized. Nineteen of these substances were quantified. The fruits of M.
multiflora presented the third largest antioxidant capacity when compared to eighteen native
fruits. Eight substances were isolated from the fruits of P. leiocarpa, characterized by
anthocyanins, phenolic acid and steroids, which were identified for the first time in fruits of this
species, three of them characterized as acylated anthocyanins previously unpublished in the
literature. Since the eight substances were identified for the first time in the fruits of this species
and three of these substances are new acylated anthocyanins. The acylated anthocyanins were
identified in P. suterella and P. nuda by comparing the retention time and UV-Vis spectrum with
the extract of P. leiocarpa.