Díaz-Chiguer Dylan L, Hernández-Luis Francisco, Nogueda-Torres Benjamín, Castillo Rafael, Reynoso-Ducoing Olivia, Hernández-Campos Alicia, Ambrosio Javier R
Departamento de Investigación, Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado, Ciudad de México, México.
Universidad Nacional Autónoma de México, Ciudad de México, México.
Mem Inst Oswaldo Cruz. 2014 Sep;109(6):757-60. doi: 10.1590/0074-0276140096. Epub 2014 Sep 9.
Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several benzimidazole derivatives. One, named JVG9 (5-chloro-1H-benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target.
克氏锥虫具有一种特殊的细胞骨架，它由微管和肌动蛋白微丝的表膜下网络组成。因此，它是开发新型抗寄生虫药物的理想靶点。苯并咪唑2-氨基甲酸酯类是一类著名的广谱驱虫药，已被证明能抑制许多原生动物的体外生长。因此，为了找到高效的抗锥虫（杀锥虫）药物，我们小组设计并合成了几种苯并咪唑衍生物。其中一种名为JVG9（5-氯-1H-苯并咪唑-2-硫醇），已发现在体外和体内条件下均对克氏锥虫血流型锥鞭毛体有效。在此，我们展示了通过激光扫描共聚焦显微镜和扫描电子显微镜观察到的JVG9对克氏锥虫锥鞭毛体的体外作用。细胞骨架蛋白的表面和分布变化与JVG9的杀锥虫活性以细胞骨架为靶点这一假设一致。
