Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, 333031, India.
Institute for Tuberculosis Research, MC-964 College of Pharmacy, University of Illino's at Chicago, 833 S. Wood St, Chicago, IL, 60621-7231, USA.
Eur J Med Chem. 2015 Nov 13;105:238-44. doi: 10.1016/j.ejmech.2015.10.024. Epub 2015 Oct 23.
Molecular hybridization is an emerging approach to design novel ligands by combination of two or more pharmacophoric subunits of known bioactive compounds. In the present study, we have designed a novel series of diarylpiperazine analogues, synthesized, characterized using FTIR, (1)H NMR, Mass, Elemental analysis and evaluated their in-vitro anti-tubercular activity. Among the reported sixteen diarylpiperazines, eleven analogues exhibited significant anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain with MIC values below 6.25 μg/mL and good selectivity index. Structure activity relationship studies concluded that, ortho-para directing group (except para chloro) substitution on ortho and para position of piperazine attached phenyl ring favored anti-tubercular activity.
分子杂交是一种新兴的方法，通过将两个或多个已知生物活性化合物的药效团亚单位组合在一起，来设计新的配体。在本研究中，我们设计了一系列新型的二芳基哌嗪类似物，通过傅里叶变换红外光谱（FTIR）、（1）H 核磁共振（NMR）、质谱（Mass）、元素分析（Elemental analysis）进行了合成和表征，并评估了它们的体外抗结核活性。在所报道的十六个二芳基哌嗪中，有十一个类似物对结核分枝杆菌 H37Rv 菌株表现出显著的抗结核活性，MIC 值低于 6.25μg/mL，且具有良好的选择性指数。构效关系研究表明，哌嗪连接的苯环上邻位和对位的对位-邻位导向基团（除对位氯外）取代有利于抗结核活性。
