Identification of novel DNA gyrase inhibitor by combined pharmacophore modeling, QSAR analysis, molecular docking, molecular dynamics, ADMET and DFT approaches.

DNA gyrase, an ATP-dependent enzyme, plays a critical role in DNA replication, transcription, and recombination in Mycobacterium tuberculosis (MTB). While fluoroquinolones are effective antibacterial agents targeting DNA gyrase, their clinical use is often limited due to side effects and the emergence of bacterial resistance. In this study, we developed a quantitative structure-activity relationship (QSAR) model to predict the anti-tubercular activity of Quinoline-Aminopiperidine derivatives targeting the DNA gyrase enzyme, using a dataset of 48 compounds obtained from the literature.