Laboratorio de Sintese de Farmacos-LASFAR, Instituto de Tecnologia em Farmacos - Farmanguinhos - Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, RJ, Brazil; Laboratório de Físico-Química de Materiais, Seção de Engenharia Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80, 22290-270 Rio de Janeiro, Brazil.
Laboratório de Físico-Química de Materiais, Seção de Engenharia Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80, 22290-270 Rio de Janeiro, Brazil.
Bioorg Med Chem Lett. 2024 Sep 15;110:129876. doi: 10.1016/j.bmcl.2024.129876. Epub 2024 Jul 2.
In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N'-((5-Nitrofuran-2-yl)methylene)-1H-benzo[d]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC/120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC/120 h = 1.520 μM, SI = 1390). Another compound (E)-N'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC/120 h of 3.600 μM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.
在这项研究中，我们设计、合成并评估了一系列苯并咪唑 N-酰腙类化合物对 T. cruzi（Y 和 Tulahuen）株和利什曼原虫属（L. amazonensis 和 L. infantum）的细胞毒性。化合物（E）-N'-((5-硝基呋喃-2-基)亚甲基）-1H-苯并[d]咪唑-2-甲酰肼对滋养体和无鞭毛体（Tulahuen 株）均表现出显著的活性，IC/120 h 为 0.033 μM，选择性指数（SI）为 7680。这比苯硝唑的效力高 46 倍（IC/120 h = 1.520 μM，SI = 1390）。另一种化合物（E）-N'-(2-羟基苯亚甲基)-1H-苯并[d]咪唑-2-甲酰肼对滋养体和无鞭毛体（Tulahuen 株）均表现出有希望的活性，IC/120 h 为 3.600 μM，SI 为 14.70。然而，它对 L. infantum 和 L. amazonensis 的疗效相对较低。这些发现为开发更有效的治疗方法提供了有价值的见解。
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