Banca de QUALIFICAÇÃO: RENATO PINTO DE SOUSA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE: RENATO PINTO DE SOUSA
DATA: 18/06/2025
HORA: 08:30
LOCAL: Auditório do PPGQ
TÍTULO: Mimosa tenuiflora (Will.) Poir.: perfil químico, semissíntese de resultados 1,2,3-triazólicos, atividade antiplasmodial e toxicidade.
PALAVRAS-CHAVES: Mimosa tenuiflora, 1,2,3-triazoles, molecular docking, antiplasmodial
PÁGINAS: 50
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
ESPECIALIDADE: Química dos Produtos Naturais
RESUMO:

Malaria is a parasitic disease that causing thousands of deaths worldwide, with Plasmodium falciparum being one of the primary culprits. Currently, some parasites have developed resistance to antimalarial drugs, highlighting the need for new antimalarials for treatment and control. This research focuses on the semisynthesis of eight new 1,4-disubstituted 1,2,3-triazole compounds (3–10) derived from N,N-Dimethyltryptamine (DMT, 1), isolated from Mimosa tenuiflora. The semisyntheses were conducted through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions and elucidated using spectrometry data (1D and 2D NMR and mass). Compound 1 was evaluated in vitro against the chloroquine-resistant W₂ strain of P. falciparum using the SYBR Green I method, and exhibited low activity (IC₅₀ = 288.4 ± 28.53 μM) compared to the positive control chloroquine (IC₅₀ = 5.8 ± 0.38 μM). However, the compound N,N-dimethyl-2-(1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-indol-3-yl)ethanamine (4) showed IC₅₀ = 4.8 ± 0.32 μM with a selectivity index ten times more active against Plasmodium compared to the human cell line used (epithelial ovarian adenocarcinoma - TOV-21G). In silico analysis of the mechanism of action of compounds 2–10 showed improved binding energy values compared to compound 1, particularly for N,N-Dimethyl-2-(1-((1-(3-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-indol-3-yl)ethanamine (7, -6.7 kcal/mol) compared to the crystallographic ligand (-6.9 kcal/mol). These findings underscore the importance of structural modifications, as the formation of new active sites enhanced the initial compounds efficiency, yielding promising candidates for antimalarial drugs.

MEMBROS DA BANCA:
Presidente - 1888044 - GERARDO MAGELA VIEIRA JUNIOR
Externo ao Programa - 1399109 - ARKELLAU KENNED SILVA MOURA
Externo ao Programa - 1731422 - JOAO SAMMY NERY DE SOUZA
Externo ao Programa - 3008542 - MICHEL MUÁLEM DE MORAES ALVES
Externo à Instituição - 110.***.***-05 - GUILHERME BARROSO LANGONI DE FREITAS - UEM