Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.
Bioorg Med Chem Lett. 2013 Nov 15;23(22):6097-105. doi: 10.1016/j.bmcl.2013.09.027. Epub 2013 Sep 16.
A series of novel arylquinoline derivatives was designed retaining significant pharmacophoric features and three dimensional geometry of bedaquiline. In silico ADME study was performed to assess drug likeness and toxicity profiles of the designed molecules. The compounds were evaluated for activity against Mycobacterium tuberculosis H37Rv using Resazurin Microtitre Assay (REMA) plate method and cytotoxicity in VERO C1008 cell line. Several of the synthesized compounds exhibited good antituberculosis activity and selectivity, especially compounds, 12i (MIC: 5.18 μM and MIC/CC50: 152.86) and 12l (MIC: 5.59 μM and MIC/CC50: 160.57). The study opens up a new platform for the development of arylquinoline based drugs for treating tuberculosis.
设计了一系列新型芳基喹啉衍生物，保留了贝达喹啉的重要药效基团和三维几何结构。进行了计算机药物代谢动力学研究，以评估设计分子的药物相似性和毒性特征。使用 Resazurin 微量滴定法（REMA）板法评估化合物对结核分枝杆菌 H37Rv 的活性，并在 VERO C1008 细胞系中评估细胞毒性。合成的几种化合物表现出良好的抗结核活性和选择性，特别是化合物 12i（MIC：5.18 μM 和 MIC/CC50：152.86）和 12l（MIC：5.59 μM 和 MIC/CC50：160.57）。该研究为开发基于芳基喹啉的治疗结核病药物开辟了新的平台。
