Molecular hybrids integrated with coumarin and oxazepane: Synthesis, biological evaluation, ADME studies and molecular docking

Novel coumarin-oxazepane hybrids 3a–b, 4a–b, 5a–b have been synthesized via a cycloaddition reaction strategy. The newly synthesized compound was confirmed based on 1H NMR, Mass and IR spectroscopic analysis techniques. Further, titled compounds were subjected to in vitro anti-microbial screening against various bacterial strains, such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. Among these, all compounds were found to be most active, equally potent against Escherichia coli and Staphylococcus aureus as compared to the standard drug penicillin. Each compound has a bioavailability score of 55% and a pain assay score of zero, complies with Lipinski’s rule of five, and has high gastrointestinal (GI) absorption. Compounds 5a and 5b show the best docking scores with (PDB IDs: 3ERD and 2DXT), ranging from −10.1 to −10.5 kcalmol−1 compared to standard Warfarin and Adriamycin and potency against HL-60 and MCF-7 cell lines in vitro.