Author/Authors :
Dيaz-Chiguer، نويسنده , , Dylan L. and Mلrquez-Navarro، نويسنده , , Adriلn and Nogueda-Torres، نويسنده , , Benjamيn and de la Luz Leَn-ءvila، نويسنده , , Gloria and Pérez-Villanueva، نويسنده , , Jaime and Hernلndez-Campos، نويسنده , , Alicia and Castillo، نويسنده , , Rafael and Ambrosio، نويسنده , , Javier R. and Nieto-Meneses، نويسنده , , Rocيo and Yépez-Mulia، نويسنده , , Liliلn and Hernلndez-Luis، نويسنده , , Francisco، نويسنده ,
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 0.014 mM (NINOA strain) and 0.32 mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC50 = 0.60 mM and LC50 = 0.78 mM, respectively; while on INC5 strain they exhibited LC50 values of 0.31 mM and 0.69 mM, 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.
