Pyrano-coumarin hybrids as potential antimicrobial agents against MRSA strains: Design, synthesis, ADMET, molecular docking studies, as DNA gyrase inhibitors

Abstract

Due to their various pharmacological effects, several substituted nitrogen heterocycles containing coumarin have recently attracted a great deal of attention. Acetyl-coumarin was used in reactions with p-methoxy-benzaldehyde, malononitrile, and ordinary heating to produce compound 1, which contains cyano-amine, allowing for the one-pot and speedy synthesis of coumarin derivatives. Ethyl cyanoacetate, triethyl orthoformate, phenyl isothiocyanate, carbon disulfide, and benzaldehyde, were used to condense compound 1 to get the corresponding chromene derivatives 2–15. Elemental and spectroscopic evidence was used to characterize every freshly synthesized hits. S. aureus (MRSA), P. aeruginosa, E. coli, and C. albicans were the standard strains employed in this investigation. Most of the compounds displayed moderate to high activity against all the tested species, according to the early screening results with a MIC range of 0.25 to 1024 μg/mL. When compared to the positive control, compounds 3, 6, 9, and 12 showed the greatest declining reduction in the bulk of the bacterial species' biofilm. The findings of subsequent testing on the three most powerful compounds against E. coli DNA gyrase inhibitory activity revealed that all these derivatives block DNA gyrase and hence prevent cell proliferation. Additionally, successful in silico investigations for the most active compounds were conducted.