Antibacterial evaluation,quantum chemical computation,and pharmacological studies of some arylidenemalononitrile and ethyl 2-cyano-3-phenylacrylate derivatives: In vitro and in silico approach

Abstract

The study emphasizes the importance of Knoevenagel condensation for forming carbon—carbon bonds to create biologically active α, β-unsaturated compounds. In this research, arylidenemalononitriles (AMN) (1–4) and ethyl 2-cyano-3-phenylacrylates (ECPA) (5–7) analogs were used to test the antibacterial efficacy against five human pathogens. Most of the compounds exhibited moderate to low inhibitory activity, whereas compounds 2 and 6 showed significant antibacterial effects, notably surpassing ampicillin in efficacy against Bacillus cereus and Escherichia coli. Molecular docking studies revealed strong binding affinities for these compounds (1–7) with bacterial proteins i.e., 1AH7 (−6.9 kcal/mol to −8.6 kcal/mol) and 6DR3 (−5.8 kcal/mol to −7.7 kcal/mol) respectively, indicating effective ligand–protein interactions. Structural analysis highlighted that specific functional groups showed enhance binding affinity, while PASS and ADMET predictions suggested favorable biological profiles for all compounds. The findings were corroborated by molecular dynamics simulations via NMA analyses and quantum chemical calculations, demonstrating strong agreement between experimental and computational results.