In-silico design, synthesis and evaluation of novel DNA-gyrase B inhibitors

2-Quinolones are an important class of compounds, isomeric to 4-quinolones. They may become promising candidates for exploiting more useful therapeutically active molecules. DNA-gyrase has drawn much attention as a selected target for finding potent anti-bacterial agents against multi-drug resistant strains such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococci pneumonia. The objective of the present study was to study the molecular docking simulations on 2-quinolone analogs as probable candidates for inhibiting DNA gyrase subunit-B of S. aureus. In the present study, docking simulations were carried out on the reported inhibitors of DNA-gyrase subunit A and B using docking software. Based on it, series of 2-quinolone analogs (compound 1-8) were designed, synthesized, characterized, and evaluated for their anti-bacterial activity against S. aureus and E. coli. Out of the eight test compounds, compound-2 showed good anti-bacterial activity against S. aureus and E. coli as compared with the rest of the other compounds. The rational approach to lead discovery has prompted a better insight into developing more specific 2-quinolones as potential antibacterial agents.