Novel Amino Derivatives and Carboxamides of Chromen‐2‐one: Synthesis, Antimicrobial Activity, and Molecular Docking Studies

Abstract In this study, a series of novel amino derivatives and carboxamides of chromen‐2‐one were synthesized and screened for their antimicrobial efficacy. Among these, compound 9 was found to be active against all pathogenic Aspergilli and exhibited a minimum inhibitory concentration (MIC) of 15.62 ‐ 31.25 µg/mL in microbroth dilution assay (MDA) and 3.91 µg/disc in disc diffusion assay (DDA). Further, compounds 10 and 13 were found to be active against pathogenic bacteria up to 1.90 µg/disc in DDA. All these active compounds were non‐toxic to human erythrocytes up to 1000 µg/mL, whereas the standard drug Amphotericin B lysed all cells at 37.50 µg/mL. The interaction with these antimicrobial results was stimulated by a molecular docking study against the sterol‐14 alpha demethylase for Aspergillus fumigatus (PDB ID ‐ 5FRB) and the peptide deformylase for Pseudomonas aeruginosa (PDB ID ‐ 1LRY). Docking showed that compounds 9, 10, and 13 exerted the strongest docking binding values against these proteins. The consistency of the binding affinity was studied using multiple sequence alignment (MSA).