In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi

Abstract

The trypanocidal effect of five benzimidazole derivatives (1–5) was determined in vitro and in vivo assays against two strains of Trypanosoma cruzi (NINOA and INC5). The in vitro trypanocidal activity was evaluated by measuring the percentage of lysis of bloodstream trypomastigotes of T. cruzi. Results point to 5-chloro-1H-benzimidazole-2-thiol (1) as the best activity profile compound with a 50% lytic concentration (LC50) of 0.014mM (NINOA strain) and 0.32mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC50=0.60mM and LC50=0.78mM, respectively; while on INC5 strain they exhibited LC50 values of 0.31mM and 0.69mM, respectively. The in vivo trypanocidal activity of 1–5 on parasitemia in a murine model acute Chagas’ disease indicated that 1 and Nfx showed similar activity on INC5 strain, while 5-chloro-1-methyl-1H-benzimidazole-2-thiol (2) and its regioisomer, 6-chloro-1-methyl-1H-benzimidazole-2-thiol (3), displayed better activity than Nfx and Bnz on NINOA strain. All compounds showed low cytotoxicity against Vero cells, with selective index 38–3000 times higher to the parasite.