Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development

Autor(es)

Santos, Benedito M. dos ^[1] ; Gonzaga, Daniel T. G. ^[2] ; da Silva, Fernando C. ^[3] ; Ferreira, Vitor F. ^[4] ; Garcia, Celia R. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, BR-05508000 Sao Paulo, SP - Brazil

^[2] Fundacao Ctr Univ Estadual Zona Oeste, Unidade Farm, BR-23070200 Rio De Janeiro, RJ - Brazil

^[3] Univ Fed Fluminense, Dept Organ Chem, Inst Chem, BR-24220900 Niteroi, RJ - Brazil

^[4] Univ Fed Fluminense, Dept Pharmaceut Technol, Pharm Sch, BR-24220900 Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMOLECULES; v. 10, n. 8 AUG 2020.
• Citações Web of Science: 1

Resumo

The 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 (mu M) and IC(50)values ranging from 2.80 mu M (9) to 29.27 mu M (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 IC(50)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. (AU)

• Processo FAPESP: 17/08684-7 - Decodificar aspectos da biologia celular e molecular do Plasmodium como uma ferramenta para desenvolver novos antimaláricos
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático