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

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.