In vitro antimicrobial combat, molecular modelling and structure activity relationship studies of novel class of aryl-ethyne tethered coumarin analogues and some 3-aryl coumarin derivatives

Abstract

A series of novel class of aryl ethyne-tethered coumarin analogues (series 1) and some 3-aryl coumarin cognates (series 2) were synthesized, and their in vitro antimicrobial activities aided by molecular modelling and the structure activity relationship (SAR) has been studied. Compounds 1e, 1g, 1h, 1m, 1o and 2e, 2f, 2g, 2h, 2i displayed excellent antimicrobial activities against the screened microbial strains with very good minimum inhibitory concentrations. Perhaps, from the present study, compounds 1g, 1e, 2f and 2h emerge out to be the most promising antimicrobial agents with MICs of 1–4 ​μg/mL. Further, molecular modelling study had also supported these outcomes by demonstrating very good binding affinities at the active site of the protein 1AI9 (Candida albicans dihydrofolate reductase - C. albicans DHFR) up to 6.24 ​kcal/mol and 5.48 ​kcal/mol, close to that of the standard drugs, iterating the possible drug like properties of some of these molecules.