In vitro and in vivo trypanocidal activity of some benzimidazole derivatives against two strains of Trypanosoma cruzi.
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 0.014 mM (NINOA strain) and 0.32 mM (INC5 strain). Reference drugs were nifurtimox (Nfx) and benznidazole (Bnz), which on NINOA strain displayed a LC(50)=0.60 mM and LC(50)=0.78 mM, respectively; while on INC5 strain they exhibited LC(50) 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.
Escuela Nacional de Ciencias Biológicas, Departamento de Parasitología, IPN, México, DF 11340, Mexico.
Dylan L
DL
Díaz-Chiguer
Adrián
A
Márquez-Navarro
Benjamín
B
Nogueda-Torres
Gloria
G
de la Luz León-Ávila
Jaime
J
Pérez-Villanueva
Alicia
A
Hernández-Campos
Rafael
R
Castillo
Javier R
JR
Ambrosio
Rocío
R
Nieto-Meneses
Lilián
L
Yépez-Mulia
Francisco
F
Hernández-Luis
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
D000981:Antiprotozoal Agents; D001562:Benzimidazoles; C031000:benzimidazole