Laís G. Ramos , Kátia R. de Souza , Juliana M.C. Barbosa , Kelly Salomão , Policarpo A. Sales Junior , Valéria R.A. Pereira , Silvane M.F. Murta , Rafaela S. Ferreira , Talita C.D. Bernardes , Solange M.S.V. Wardell , James L. Wardell , Nubia Boechat , Samir A. Carvalho
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引用次数: 0
摘要
在本研究中,我们介绍了一系列苯并咪唑 N-酰肼类化合物的设计、合成和细胞毒性评估,这些化合物对克鲁斯原虫(Y 和 Tulahuen)和利什曼原虫(亚马逊利什曼原虫和婴儿利什曼原虫)菌株具有抑制作用。化合物(E)-N'-((5-硝基呋喃-2-基)亚甲基)-1H-苯并[d]咪唑-2-甲酰肼对胰原体和非胰原体(Tulahuen 株)均表现出显著的活性,IC50/120 h 为 0.033 μM,选择性指数(SI)为 7680。其效力是苯并咪唑(IC50/120 h = 1.520 μM,SI = 1390)的 46 倍。另一种化合物 (E)-N'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide 对胰原体和非胰原体形式(Tulahuen 株)都显示出良好的活性,IC50/120 h 为 3.600 μM,SI 为 14.70。然而,它对婴儿淋巴细胞和亚马逊淋巴细胞的疗效相对较低。这些发现为开发更有效的克氏锥虫治疗方法提供了宝贵的启示。
Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum
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 IC50/120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 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 IC50/120 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.
期刊介绍:
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.