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合成及抗结核喹啉腙类化合物的二元定量构效关系研究。

Synthesis and binary QSAR study of antitubercular quinolylhydrazides.

机构信息

National Facility for Drug Discovery, Department of Chemistry, Saurashtra University, Rajkot 360005, Gujarat, India.

出版信息

Bioorg Med Chem Lett. 2013 Sep 1;23(17):4896-902. doi: 10.1016/j.bmcl.2013.06.076. Epub 2013 Jul 3.

Abstract

In continuation with our previous work in anti-TB research area, in the present study we have demonstrated the structural diversity of quinolylhydrazides as potent anti-tuberculars. The compound library was synthesized by molecular hybridization approach and tested in vitro against Mycobacterium tuberculosis H37Rv strains. Among the designed conjugates, the most promising molecules were found to exhibit 100% Growth Inhibition (GI) at MIC <6.25 μg/mL. Moreover, several analogs in the designed series were also turned out as excellent anti-tuberculars. To probe the structural characteristics influencing on the SAR, the classification model was generated using a binary QSAR approach termed recursive partitioning (RP) analysis. The significant features outlined by the RP model act as a guide in order to design the 'lead' compound.

摘要

延续我们之前在抗结核研究领域的工作,本研究表明了喹喔啉腙作为潜在的抗结核药物具有结构多样性。通过分子杂交方法合成了化合物库,并在体外针对结核分枝杆菌 H37Rv 株进行了测试。在所设计的缀合物中,最有前途的分子在 MIC <6.25 μg/mL 时表现出 100%的生长抑制(GI)。此外,所设计系列中的几个类似物也被证明是优秀的抗结核药物。为了研究结构特征对 SAR 的影响,使用称为递归分区(RP)分析的二元 QSAR 方法生成分类模型。RP 模型突出的显著特征可以作为设计“先导”化合物的指南。

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