TY - JOUR
T1 - In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi
AU - Díaz-Chiguer, Dylan L.
AU - Márquez-Navarro, Adrián
AU - Nogueda-Torres, Benjamín
AU - de la Luz León-ávila, Gloria
AU - Pérez-Villanueva, Jaime
AU - Hernández-Campos, Alicia
AU - Castillo, Rafael
AU - Ambrosio, Javier R.
AU - Nieto-Meneses, Rocío
AU - Yépez-Mulia, Lilián
AU - Hernández-Luis, Francisco
N1 - Funding Information:
This work was supported by project 80093 from CONACyT, IN201510 from DGAPA-UNAM, and IX200610 from DGAPA-IXTLI-UNAM. Dylan L. Diaz-Chiguer was supported by a doctoral fellowship (32972) from CONACyT. We thank Olivia Reynoso-Ducoing and Erick Suárez for general technical assistance.
PY - 2012/4
Y1 - 2012/4
N2 - 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 (LC 50) of 0.014mM (NINOA strain) and 0.32mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC 50=0.60mM and LC 50=0.78mM, respectively; while on INC5 strain they exhibited LC 50 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.
AB - 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 (LC 50) of 0.014mM (NINOA strain) and 0.32mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC 50=0.60mM and LC 50=0.78mM, respectively; while on INC5 strain they exhibited LC 50 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.
KW - Benzimidazole derivative
KW - Chagas's disease
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=84857115113&partnerID=8YFLogxK
U2 - 10.1016/j.actatropica.2011.12.009
DO - 10.1016/j.actatropica.2011.12.009
M3 - Artículo
C2 - 22212465
SN - 0001-706X
VL - 122
SP - 108
EP - 112
JO - Acta Tropica
JF - Acta Tropica
IS - 1
ER -