Antimicrobial assessment and computational investigation of newly designed and synthesized Schiff base of chloroformylated chromene-sulfonamide derivatives against bacterial DNA gyrase

Abstract

Antimicrobial resistance, being listed among the top 10 threats globally, not only costing both health systems and national economies overall, but also forcing antimicrobial drug development pipeline to shake and break, pointing out the need for developing new drug candidates that overcome resistance. The present study represents the antibacterial assessment of newly designed and synthesized Schiff base derivatives of chloroformylated chromene-sulfonamides. Applying a combination of synthetic chemistry and extensive computational investigations, the structural properties and biological activities of the synthesized chromene-sulfonamides have been assessed. Molecular docking and density functional theory (DFT) studies were performed to explore the interaction of the synthesized chromene-sulfonamide derivatives with bacterial DNA gyrase, a crucial target for antibiotic development. Our findings indicate that several Schiff bases have foremost binding affinities and favourable interaction profiles with DNA gyrase, signifying their potency as novel antimicrobial agents. In vitro antimicrobial assay further demonstrated the efficacy of the synthesised compounds against various bacterial strains including resistant K. pneumoniae, highlighting their promising role in combating antibiotic resistance. Among the series, compound bearing sulfadoxine (5d) and, sulfamethoxazole (5g) showed potency better than standard antibiotic, novobiocin. This study underscores the importance to integrate computational approaches with experimental validations in the discovery of new therapeutic agents against bacterial infections.