Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

Background: Tuberculosis is evidently a major health threat among human populations worldwide. The current study presents the synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a-o) as potential Mycobacterium tuberculosis DNA gyrase inhibitors. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. With this in mind, the synthesized derivatives (4a-o) were subjected to in vitro antitubercular evaluation by the MABA method and were tested for MTB DNA gyrase inhibition by supercoiling assay. Results: All the synthesized compounds displayed inhibition of MTB within the MIC range of 1.56-12.5 mu M. Further, out of the selected compounds that underwent DNA gyrase inhibition, compound 4o proved to be a potent lead molecule by displaying 82% of enzyme inhibition at 1 mu M. All the synthesized derivatives also underwent molecular docking studies to comprehend their hypothetical binding interactions with Mycobacterium smegmatis GyrB. Conclusion: All the results suggested that most of the synthesized derivatives inhibited Mycobacterium tuberculosis, and some 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs could act as leads for the development of antitubercular agents.