2. Academic Validation
  3. Discovery of 1,3-Disubstituted Pyrazole derivatives as Mycobacterium tuberculosis inhibitors

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

  • Bioorg Med Chem Lett. 2025 Feb 28:121:130156. doi: 10.1016/j.bmcl.2025.130156.
Guoquan Wan 1,  Chao Gao 2,  Xiaorui Zhang 3,  Huapei Qiu 1,  Qifan Tang 1,  Jumei Zeng 4,  Luoting Yu 5
Affiliations

Affiliations

  • 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 West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China. Electronic address: zengjumei@scu.edu.cn.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China; Children's Medicine Key Laboratory of Sichuan Province, Chengdu 610041, China. Electronic address: yuluot@scu.edu.cn.
PMID: 40024479 DOI: 10.1016/j.bmcl.2025.130156
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.

Keywords

1,3-disubstituted pyrazole derivative; SAR; Tuberculosis.

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