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Triazol-derivatives as novel antimalarials.
Benedito Matheus dos Santos
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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Create a topicThe search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite Plasmodium falciparum in a culture of fifty-four triazole compounds derived from 1H-and 2H-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (µM) and IC50 values ranging from 2.80 µM (9) to 29.27 µM (21). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for P. falciparum G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC50 values for the knockout strain. The cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (9, 13, 19, 22, 24, 29), showed no toxicity at the tested concentrations.
Emmanuel Dias da Silva
Olá, Benedito
Parabéns pelo trabalho e por sua apresentação. Abraço
Bruna Katiele de Paula Sousa
Parabéns pelo trabalho! Gostaria de saber qual foi o valor de limite de atividade para os compostos ativos, foi abaixo de 10 uM? E também gostaria de saber se futuramente este trabalho irá identificar o alvo molecular em plasmodium, para ação desses triazóis. Obrigada.
Benedito Matheus dos Santos
Obrigado, para avaliação da atividade antimalárica utilizamos diferentes concentrações dos compostos partindo de 50 µM, dos compostos que apresentaram atividade antimalárica nesta faixa avaliada 10 resultaram em valores e IC50 (concentração capaz de exterminar 50% da parasitemia quando comparado ao controle) abaixo de 10 µM. Com relação ao alvo destes compostos temos planos futuros de avaliar novos compostos oriundos de síntese baseada nos compostos mais ativos identificados neste trabalho, e sim tentaremos elucidar o mecanismo de ação bem como o potencial alvo.
Segue o link do trabalho apresentado em questão: https://doi.org/10.3390/biom10081197
Abraço.
Bruna Katiele de Paula Sousa
Que bom Benedito!! Obrigada por compartilhar o artigo. Sucesso e abraços.
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Benedito Matheus dos Santos
Olá, muito obrigado. Abraço