Departamento de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de la República, Igua 4225, 11400 Montevideo, Uruguay.
Eur J Med Chem. 2009 Nov;44(11):4426-33. doi: 10.1016/j.ejmech.2009.06.014. Epub 2009 Jun 18.
Exploring the influence of different substitution patterns of 2H-benzimidazole 1,3-dioxide derivatives (BzNO) we prepared fifteen new derivatives. Initially the BzNO were tested against Trypanosoma cruzi Tulahuen 2 strain epimastigote form rendering very potent anti-T. cruzi agents. Moreover, the BzNO were able to inhibit the growth of virulent and resistant to Benznidazole strains (CL Brener clone, Colombiana, and Y strains) and to Leishmania braziliensis. Interestingly, BzNO exhibited very high selectivity index and particularly the spiro-BzNO 13 provokes an important diminution of amastigotes in Vero cells. Besides, it was found a diminution of acetate and glycine as excreted metabolites but without increase of parasite glucose uptake indicating that the glycosome is probably not involucrate in the 2H-benzimidazole 1,3-dioxides mechanism of action.
我们制备了十五种新的 2H-苯并咪唑 1,3-二氧化物（BzNO）衍生物，探讨了不同取代模式对其的影响。最初，BzNO 对 Trypanosoma cruzi Tulahuen 2 株前鞭毛体进行了测试，结果显示它们是非常有效的抗 T. cruzi 药物。此外，BzNO 能够抑制有致病性和对 Benznidazole 耐药的菌株（CL Brener 克隆、Colombiana 和 Y 株）以及 Leishmania braziliensis 的生长。有趣的是，BzNO 表现出非常高的选择性指数，特别是螺环-BzNO 13 可引起 Vero 细胞中无鞭毛体的显著减少。此外，发现乙酸盐和甘氨酸的排泄代谢物减少，但寄生虫葡萄糖摄取没有增加，表明糖体可能不参与 2H-苯并咪唑 1,3-二氧化物的作用机制。
