Banca de DEFESA: BRUNA CAROLINE ESTEVES DE SOUZA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : BRUNA CAROLINE ESTEVES DE SOUZA
DATE: 17/09/2024
TIME: 13:00
LOCAL: IQ sala 49
TITLE:

DESIGN, SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF MANNICH BASES DERIVED FROM LAUSONE: POTENTIAL ANTIMALARIAL AND ANTICHOLINESTERATIC AGENTS

KEY WORDS:

Lausona, Mannich bases, cholinesterases, malaria

PAGES: 288
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

The naphthoquinone lawsone, an orange dye extracted from the leaves of the henna plant, is widely used for coloring hair and skin. It also plays a significant role in organic synthesis, particularly in the multicomponent Mannich reaction with amines and aldehydes, yielding compounds known as Mannich bases. These compounds are noteworthy for their structural diversity and diverse biological activities, including the inhibition of the enzyme acetylcholinesterase, which is relevant in the treatment of Alzheimer's disease. Alzheimer's disease is characterized by disruptions in neuronal communication with synapses, leading to impaired memory and cognitive function. Additionally, Mannich bases exhibit antiparasitic activity, particularly against malaria, a parasitic disease caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitoes.
Although established treatments exist for both malaria and Alzheimer's disease, these treatments are often associated with side effects and, in the case of malaria, with issues related to drug resistance. Consequently, there is a persistent need for new therapeutic alternatives. This research aims to contribute to the discovery of new compounds with therapeutic potential for these diseases. Sixteen new Mannich bases derived from lawsone were synthesized, with potential for cholinesterase inhibition and antimalarial activity. The structural design was
guided by two main strategies: bioisosterism and homologation, inspired by the drugs donepezil, a cholinesterase inhibitor, and atovaquone, an antimalarial agent.
The synthesis was carried out using the multicomponent Mannich reaction with lawsone, three aldehydes (formaldehyde, acetaldehyde, and benzaldehyde), and eight different amines. The reactions were performed following the principles of green chemistry, with purification achieved through recrystallization, resulting in final yields ranging from 30% to 90%. To enhance solubility, the Mannich bases were converted into hydrochlorides, with high
purity confirmed by High-Performance Liquid Chromatography (HPLC). The structures were elucidated using Mass Spectrometry and Nuclear Magnetic Resonance (NMR) spectroscopy of Hydrogen (¹H) and Carbon (¹³C).
The hydrochlorides were evaluated for their enzyme inhibition percentages against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, LaDMol377 hydrochloride demonstrated a promising inhibition profile against AChE, encouraging further enzymatic studies. The antimalarial activity of the hydrochlorides is currently under evaluation, with results eagerly anticipated

COMMITTEE MEMBERS:
Presidente - 1700480 - ARTHUR EUGEN KUMMERLE
Interno - 2624418 - CLAUDIO EDUARDO RODRIGUES DOS SANTOS
Externo ao Programa - 1221906 - LUCIANO RAMOS SUZART - UFRRJExterno à Instituição - DANIEL PAIS PIRES VIEIRA - IFRJ
Externa à Instituição - MARINA AMARAL ALVES - UFRJ