Abstract
The briskened urge to develop potential antibacterial candidates against multidrug-resistant pathogens has motivated the present research study. Herein, newly synthesized coumarin derivatives with azomethine and amino-methylated as the functional groups have been focused on their antibacterial efficacy. The study proposed two distinct series: 3-acetyl substituted coumarin derivatives, followed by the Schiff base approach (5a-5i), and formaldehyde-secondary cyclic amine-based derivatives (7a-7g), using the Mannich base approach, further the compounds have been confirmed through various spectral studies. Further, target-specific binding affinity has been affirmed via in silico study. In vitro antibacterial study suggested compounds 5d and 5f to be most effective against S. aureus and multidrug-resistant K. pneumoniae, with MIC values of 8 and 16 μg mL(-1). Among them, the compounds 5d and 5f showed excellent binding scores against different bacterial gyrase compared to the standard novobiocin. Based on RMRS, RMSF, Rg, and H-bond plots, MD simulation study at 100 ns also suggested better stability of 5d inside gyraseB of E. coli than the complex of E. coli-GyrB-novobiocin. The toxicity and pharmacokinetic profiles showed favorable drug-likeness. Overall, systematic in vitro and in silico assessment suggested that multimodal antibacterial derivatives 5d and 5f strongly inhibit both bacterial DNA gyrase and biofilm formation of drug-resistant pathogens, suggesting their potency in mainstream antibacterial therapy.