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微波辅助区域选择性合成喹啉取代三唑作为有效的抗结核和抗真菌剂通过铜(I)催化环加成。

Microwave assisted regioselective synthesis of quinoline appended triazoles as potent anti-tubercular and antifungal agents via copper (I) catalyzed cycloaddition.

机构信息

Department of Studies in Chemistry, Karnatak University Dharwad 580003, India.

Department of Studies in Chemistry, Karnatak University Dharwad 580003, India.

出版信息

Bioorg Med Chem Lett. 2021 Jun 1;41:127984. doi: 10.1016/j.bmcl.2021.127984. Epub 2021 Mar 22.

Abstract

Quinolin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones 8j-v were synthesized by click chemistry as an ultimate tactic where [3 + 2] cycloaddition of azides with terminal alkynes has been evolved. Herein, we are inclined to divulge the implication and prevalence of CuSO·5HO and THF/water promoted [3 + 2] cycloaddition reactions. The foremost supremacy of this method are transitory reaction times, facile workup, excellent yields (88-92%) with exorbitant purity and regioselective single product formation both under conventional and microwave method. Docking studies illustrated strong binding interactions with enzyme InhA-D148G (PDB ID: 4DQU) by means of high C-score values. The anti-tubercular and antifungal screening of synthesized compounds proclaimed promising activity. The in vitro and in silico studies imply that these triazoles appended quinolines may acquire the ideal structural prerequisites for auxiliary expansion of novel therapeutic agents.

摘要

3-取代-1,2,3-三唑并[1,5-a]嘧啶-7-酮 8j-v 通过点击化学法合成,其中叠氮化物与末端炔烃的[3+2]环加成反应是最终策略。在此,我们倾向于揭示 CuSO·5HO 和 THF/水促进[3+2]环加成反应的意义和普遍性。该方法的主要优势是反应时间短、操作简单、产率高(88-92%)、纯度高,并且在常规和微波条件下均以区域选择性单产物的形式形成。对接研究表明,通过高 C 分数值与酶 InhA-D148G(PDB ID:4DQU)具有强烈的结合相互作用。合成化合物的抗结核和抗真菌筛选显示出有希望的活性。体外和计算研究表明,这些三唑并取代的喹啉可能获得辅助扩展新型治疗剂的理想结构前提。

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