Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Departamento de Síntese Orgânica, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil.
J Med Chem. 2011 Sep 8;54(17):5988-99. doi: 10.1021/jm2003624. Epub 2011 Aug 15.
The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Derivatives of isoniazid (INH), (E)-N'-[(1-aryl)-1H-1,2,3-triazole-4-yl)methylene] isonicotinoyl hydrazides, exhibited significant activity with MIC values ranging from 2.5 to 0.62 μg/mL. In addition, they displayed low cytotoxicity against liver cells (hepatoma HepG2) and kidney cells (BGM), thereby providing a high therapeutic index. The results demonstrated the potential and importance of developing new INH derivatives to treat mycobacterial infections.
本研究旨在使用点击化学制备各种 4-取代的 N-苯基-1,2,3-三唑衍生物。采用 Alamar Blue 敏感性试验，对衍生物进行体外抗结核分枝杆菌 H37Rv（ATCC 27294）的抗菌活性筛选。活性以最小抑菌浓度（MIC）表示，单位为 μg/mL（μM）。异烟肼（INH）的衍生物，（E）-N'-[(1-芳基)-1H-1,2,3-三唑-4-基）亚甲基]异烟酰基酰肼，表现出显著的活性，MIC 值范围为 2.5 至 0.62 μg/mL。此外，它们对肝（肝癌 HepG2）和肾（BGM）细胞的细胞毒性较低，从而提供了较高的治疗指数。结果表明，开发新的 INH 衍生物治疗分枝杆菌感染具有潜力和重要性。
