One-Pot Synthesis of Novel 3-{(1H-Benzo[d]Imidazol-2-yl)Amino(Phenyl)Methyl}Benzofuran-2(3H)-Ones as Antimicrobial Agents and Their Molecular Docking Studies

Abstract

Aminobenzimidazole-coumaranone conjugates, specifically 3-{[(1H-benzo[d]imidazol-2-yl)amino](substitutedphenyl)methyl}benzofuran-2(3H)-ones, were synthesized through a one-pot reaction involving 2-coumaranone, aryl aldehydes, and 2-aminobenzimidazole. This reaction, catalyzed by triethylamine in acetonitrile at 80°C, achieved yields of up to 85%. Preparative liquid chromatography successfully isolated compounds 4b and 4c as two isomers with purities reaching 99.30%. Their absolute configurations, (S, R) for compound 4b and (R, S) for compound 4c, were determined using electronic circular dichroism and confirmed via TD-DFT calculations. The antimicrobial potential of the synthesized compounds (4a–j) and their enantiopure isomers (4b′, 4b″, 4c′, 4c″) was evaluated against the bacterial strains Bacillus subtilis, Staphylococcus aureus, Staphylococcus proteolyticus, and the fungal strains Candida albicans and Aspergillus niger. Notably, compounds 4a, 4d, 4i, and 4j exhibited superior antimicrobial activity. Molecular docking studies further reinforced these results, revealing strong receptor binding affinities (−7.5 to −10.5 kcal/mol), which surpass those of standard drugs. These findings highlight the promising potential of aminobenzimidazole-coumaranone conjugates as effective antimicrobial agents.