Escuela Nacional de Ciencias Biológicas, Departamento de Parasitología, IPN, México, DF 11340, Mexico.
Acta Trop. 2012 Apr;122(1):108-12. doi: 10.1016/j.actatropica.2011.12.009. Epub 2011 Dec 27.
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.
五种苯并咪唑衍生物（1-5）的杀锥虫效果在针对两种 Trypanosoma cruzi（NINOA 和 INC5）株的体外和体内试验中进行了测定。通过测量锥虫血淋巴鞭毛体的裂解百分比来评估体外杀锥虫活性。结果表明，5-氯-1H-苯并咪唑-2-硫醇（1）是具有最佳活性谱的化合物，对 NINOA 株的 50%裂解浓度（LC（50））为 0.014 mM，对 INC5 株的 LC（50）为 0.32 mM。参考药物为硝呋替莫（Nfx）和苯并咪唑（Bnz），它们对 NINOA 株的 LC（50）分别为 0.60 mM 和 0.78 mM；而对 INC5 株的 LC（50）分别为 0.31 mM 和 0.69 mM。在急性恰加斯病的小鼠模型中，1-5 对寄生虫血症的体内杀锥虫活性表明，1 和 Nfx 对 INC5 株表现出相似的活性，而 5-氯-1-甲基-1H-苯并咪唑-2-硫醇（2）及其区域异构体 6-氯-1-甲基-1H-苯并咪唑-2-硫醇（3）对 NINOA 株的活性优于 Nfx 和 Bnz。所有化合物对 Vero 细胞的细胞毒性均较低，对寄生虫的选择性指数为 38-3000 倍。
