Synthesis, anti-microbial evaluation, and in silico studies of novel quinoline-isoxazole hybrids

A series of novel quinoline-isoxazole hybrids 6a–o has been synthesized via multistep synthetic approach involving hetero Diels-alder reaction strategy. The target compounds were obtained in good yield, using low-cost readily available starting materials using simple reaction conditions. The newly synthesized compounds were confirmed using ¹H NMR,¹³C NMR, and Mass spectroscopic analysis techniques. Further, compounds 6a–o were subjected to in vitro antimicrobial screening against various bacterial and fungal strains, such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Aspergillus niger, and Candida albicans. Among these, compounds 6i, 6j, and 6 l were found most active having equally potent compared to standard drug Ampicillin and Gentamycin. Moreover, in silico studies of 6a–o with E. coli DNA gyrase through molecular docking and MD simulations showed excellent binding properties of these derivatives with protein site.