Synthesis, molecular docking, ADMET studies and antimicrobial activities of coumarin-chalcone hybrid derivatives

The exploitation of naturally derived drugs can become a replacement for ineffective drugs due to the relentless antimicrobial resistance. A series of natural-product-based coumarin-chalcones (4a-4i) were synthesised via facile Steglich esterification. The coumarin-chalcones (4a-4i) showed effective inhibition against P. aeruginosa (7-13 mm) and E. coli (8-12 mm) in comparison to the standard drug ampicillin and coumarin alone. Compounds 4b and 4g exhibited the highest inhibition zone against P. aeruginosa (13 mm) and E. coli (12 mm) respectively. The hybridisation of chalcone in the coumarin network introduced active C = CH, C = O and C-O moieties, contributing to significant microbial inhibition. The molecular docking of 4b exhibited the highest binding affinity -10.1 kcal/mol as compared to 4a, 4c and 4g -9.2 kcal/mol, -9.2 kcal/mol and -9.1 kcal/mol respectively. The ADMET studies also supported natural-product-based coumarin-chalcones as suitable drug candidates. This study is noteworthy for coumarin-based drug development in the medicinal field.