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Discovery of 1,3-Disubstituted Pyrazole derivatives as Mycobacterium tuberculosis inhibitors

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机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China [2]Institute of Immunology and Inflammation,Frontiers Science Center for Disease-related Molecular Network,West China Hospital, Sichuan University, Chengdu 610041, China [3]West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China [4]Children’s Medicine Key Laboratory of Sichuan Province, Chengdu 610041, China
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关键词: 1 3-disubstituted pyrazole derivative SAR Tuberculosis

摘要:
Tuberculosis is a global epidemic caused by Mycobacterium tuberculosis, predominantly impacting underprivileged regions worldwide. Here, we identified a novel 1,3-disubstituted pyrazole derivative, compound A, that exhibits antitubercular activity through in vitro screening. Further SAR studies resulted in the identification of compounds 4c and 6b, which exhibited improved antitubercular activity, with MIC values of 5.34 and 5.04 μg/mL against H37Ra, respectively. Additionally, compounds 4c and 6b exhibited favorable safety profiles, showing no obvious toxicity to Vero, A549, and HepG2 cell lines. Our docking studies suggest that PptT may serve as one of the potential targets for these compounds. These encouraging results provide valuable insights for the development of novel structured antitubercular agents.Copyright © 2024. Published by Elsevier Ltd.

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出版当年[2025]版:
大类 | 4 区 医学
小类 | 2 区 有机化学 4 区 药物化学
最新[2025]版:
大类 | 4 区 医学
小类 | 2 区 有机化学 4 区 药物化学
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第一作者机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China
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通讯机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China [4]Children’s Medicine Key Laboratory of Sichuan Province, Chengdu 610041, China
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