Antimicrobial activity and ADMET analysis of novel coumarin-based pyridine and pyran hybrids

Abstract

Abstract A series of novel pyridine and pyran incorporated chromene moiety have been synthesized using 6-(2-(4-nitrophenyl) diazenyl)-3-acetyl-2 H-chromen-2-one 1 as the starting material. The chemical structures of the newly synthesized derivatives were characterized using different spectroscopic techniques (FT-IR, 1 HNMR and 13 CNMR) and elemental analysis. All derivatives were assessed for their in vitro antimicrobial activity against six clinically isolated multi-drug resistance strains, including Gram-positive ( Bacillus pumilis , Streptococcus faecalis ) and Gram-negative ( Escherichia coli , Enterobacter cloacae ) bacteria and fungi ( Saccharomyces cerevisiae , Candida albicans ) using broth microdilution and agar well-diffusion technique assays. The synthesized compounds exhibited moderate to good antimicrobial activity against the tested strains, with several derivatives approaching, and in one instance matching, the potency of the reference drugs. Notably, 2a , 5a , 5b , 6b , 7b , and 8a derivatives merged as the most promising bactericidal and fungicidal agents Compound 5a demonstrated an excellent activity toward S. faecalis which is equal to Penicillin G. with MIC value (3.91 µg/ml) and MBC value (31.3 µg/ml). Furthermore, compounds 5b , 6b , 7b and 8a revealed an excellent potency against S. faecalis with MIC value (7.81 µg/ml) and bactericidal activity with MBC value from 15.6 to 62.5 µg/ml Furthermore, in-silico ADMET analysis of compounds 6a , 6b , 8a , and 8b demonstrated adherence to Pfizer’s guidelines, reflecting favorable physicochemical properties.