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新型吲哚醇-1,2,3-三唑衍生物的设计与合成及其作为潜在抗结核和抗菌药物的研究。

Design and synthesis of new indanol-1,2,3-triazole derivatives as potent antitubercular and antimicrobial agents.

机构信息

Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413 501, MS, India.

Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, MS, India.

出版信息

Bioorg Med Chem Lett. 2020 Nov 15;30(22):127579. doi: 10.1016/j.bmcl.2020.127579. Epub 2020 Sep 25.

Abstract

In a search of new antitubercular agents, herein we have reported a series of new thirty-two indanol-1,2,3-triazole derivatives. The synthesized compounds were screened for their in vitro antitubercular and antimicrobial activities. Among the screened compounds, most of the compounds have displayed good antitubercular activity against Mycobacterium tuberculosis H37Rv. The compound 5g has been identified as potent antitubercular agent with MIC value 1.56 µM. The most active compounds of the series were further studied for their cytotoxicity against HEK 293 cells using MTT assay and found to be nontoxic. In addition, ten compounds were shown good antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study against Mycobacterial enoyl-ACP-reductase (InhA) was performed to gain an insight into the molecular mechanism of antitubercular action. The pharmacokinetic parameters of these compounds were studied and displayed acceptable drug-likeness score.

摘要

在寻找新的抗结核药物的过程中,我们在此报道了一系列新的三十二个吲唑-1,2,3-三唑衍生物。合成的化合物进行了体外抗结核和抗菌活性筛选。在所筛选的化合物中,大多数化合物对结核分枝杆菌 H37Rv 表现出良好的抗结核活性。化合物 5g 被确定为具有 MIC 值 1.56µM 的有效抗结核剂。该系列中最具活性的化合物进一步用 MTT 法进行了对 HEK 293 细胞的细胞毒性研究,结果显示无细胞毒性。此外,有 10 种化合物对细菌和真菌病原体均表现出良好的抗菌活性。对分枝杆菌烯酰-ACP 还原酶(InhA)进行了分子对接研究,以深入了解抗结核作用的分子机制。对这些化合物的药代动力学参数进行了研究,结果显示它们具有可接受的类药性评分。

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