Pyrazinoates as antiparasitic agents against Trypanosoma cruzi

Autor(es)

Vasconcelos, Camilla I. ^[1] ; Varela, Marina T. ^[1] ; Torrecilhas, Ana C. ^[1] ; Fernandes, Joao P. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIV DER PHARMAZIE; v. 351, n. 11 NOV 2018.
• Citações Web of Science: 0

Resumo

This work reports a repurposing study of pyrazinoic acid (1) and methyl (2), ethyl (3) and 2-chloroethyl (4) ester derivatives with antimycobacterial activity, in assays against Trypanosoma cruzi. The compounds and benznidazole, the standard antitrypanosoma drug, were evaluated in concentrations ranging from 100 to 6.25 mu g/mL. The results showed that compounds 2 and 3 (EC50 = 182 and 447 mu M) significantly reduced the infection rate of the parasite into the mammalian cells at 100 mu g/mL (p < 0.05) in a similar way to benznidazole. In addition, all the compounds also significantly reduced the number of intracellular parasites (compound 1 at 50 mu g/mL, and compounds 2-4 at 100 mu g/mL, p < 0.05) in comparison to the control. Compounds 1 and 2 were more effective than benznidazole at 50 mu g/mL (p < 0.001). Moreover, compounds 1-4 did not show significant cytotoxicity against THP-1, J774, and HeLa cells (>1000 mu M), indicating that they possess considerable selectivity against the parasites. This report represents the first study of such compounds against T. cruzi, indicating the potential of pyrazinoates as antiparasitic agents. (AU)

• Processo FAPESP: 16/01917-3 - O papel imunomodulatório das vesículas extracelulares liberadas por macrófagos infectados pelo Trypanosoma cruzi
• Beneficiário: Ana Claudia Trocoli Torrecilhas
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/03918-2 - Avaliação da atividade antiparasitária e da citotoxicidade de derivados de produtos naturais em Trypanosoma cruzi: planejamento e síntese de análogos potencialmente superiores
• Beneficiário: Marina Themoteo Varela
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/25028-3 - Anti-histamínicos H3R/H4R como agentes pró-cognitivos: uma abordagem multialvo
• Beneficiário: João Paulo dos Santos Fernandes
• Modalidade de apoio: Auxílio à Pesquisa - Regular