Molecular Docking and Structure–Activity Relationship Study of Polyphenols with Antibacterial and Antibiotic-Modulating Properties

Abstract

The antibacterial activity of 18 phenolic compounds, including flavonoids and phenolic acids, against organisms of Escherichia coli, Klebsiella pneumoniae, and Proteus vulgaris that are resistant to several drugs was assessed in this study using the agar diffusion method. The strain’s strong resistance was confirmed by antibiotic susceptibility testing, which used fourteen drugs and only found inhibition zones for five of them. Out of the polyphenols, four compounds were effective against P. vulgaris, five against K. pneumoniae, and twelve against E. coli bacteria. The greatest inhibitory zone (18.75 ± 0.25 mm) against E. coli was shown by propyl gallate, an ester of gallic acid. Activity was significantly impacted by structural changes. Propyl substitution increased antibacterial activities across all strains, while methoxy substitution decreased them. The antibacterial effectiveness was reduced by the hydroxylation of flavonoids and the C3–C4 dihydroxylation of cinnamic acid. Propyl gallate primarily had antagonistic effects, while combination experiments demonstrated additive, synergistic, and antagonistic interactions. Propyl gallate (ΔG = −7.5 kcal/mol) exhibited substantial binding affinities with TEM-1 and NDM-1 β-lactamases via hydrogen and hydrophobic interactions, according to molecular docking. These results demonstrate propyl gallate as a viable antibacterial adjuvant option and validate the structure–activity relationship of phenolic compounds.