Banca de DEFESA: FELIPE PIRES MACHADO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : FELIPE PIRES MACHADO
DATE: 25/01/2024
TIME: 09:00
LOCAL: PPGQ, IQ - UFRRJ
TITLE:

Synthesis, Characterization and In Silico and In Vitro Evaluation of the Anti-leukemia Effect of Tetra-substituted Pyrazoles on Jurkat Cells

KEY WORDS:

Pyrazole. Heterocyclic compounds. Microwave synthesis. Antileukemic activity

PAGES: 125
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Química Orgânica
SPECIALTY: Síntese Orgânica
SUMMARY:

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.

COMMITTEE MEMBERS:
Presidente - ***.742.388-** - AUREA ECHEVARRIA AZNAR NEVES LIMA - USP
Interna - 1177598 - ROSANE NORA CASTRO
Externo à Instituição - FELIPE VITORIO RIBEIRO - SEE