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

IF 2.2 4区医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-06-01 Epub Date: 2025-02-28 DOI:10.1016/j.bmcl.2025.130156

Guoquan Wan , Chao Gao , Xiaorui Zhang , Huapei Qiu , Qifan Tang , Jumei Zeng , Luoting Yu

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Abstract

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.

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1,3-二取代吡唑衍生物结核分枝杆菌抑制剂的发现。

结核病是由结核分枝杆菌引起的全球性流行病，主要影响世界各地的贫困地区。在这里，我们通过体外筛选发现了一种新型 1,3-二取代吡唑衍生物--化合物 A，它具有抗结核活性。进一步的 SAR 研究发现了化合物 4c 和 6b，它们的抗结核活性有所提高，对 H37Ra 的 MIC 值分别为 5.34 和 5.04 μg/mL。此外，化合物 4c 和 6b 还具有良好的安全性，对 Vero、A549 和 HepG2 细胞系没有明显毒性。我们的对接研究表明，PptT 可能是这些化合物的潜在靶点之一。这些令人鼓舞的结果为开发新型结构抗结核药物提供了宝贵的启示。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.