Design, Synthesis and Structure Activity Relationship of Novel Benzimidazole Derivatives as Potent Antimicrobial Agents
Keywords:
Benzimidazole derivatives, antimicrobial activity, HOMO–LUMO analysis, Structure activity relationship (SAR)Abstract
The growing challenge of antimicrobial resistance necessitates the discovery of novel therapeutic scaffolds with improved potency and specificity. In this study, a focused library of benzimidazole derivatives was rationally designed, synthesized, and evaluated to explore their potential as antimicrobial agents. The synthetic strategy involved a three-step process condensation of o-phenylenediamine with substituted aromatic aldehydes, followed by diazo coupling and further functionalization yielding structurally diverse derivatives in good yields (75–82%). Structural characterization using ^1H and ^13C NMR, FTIR, mass spectrometry, and elemental analysis confirmed the chemical integrity and purity of all compounds. In vitro antimicrobial screening revealed that derivatives bearing electron-withdrawing substituents, notably BI-2 (–Cl) and BI-3 (–NO₂), exhibited enhanced activity with minimum inhibitory concentrations (MICs) as low as 31.25 µg/mL against Staphylococcus aureus and 62.5 µg/mL against Escherichia coli. Complementary computational studies, including molecular docking and density functional theory (DFT) calculations, provided insight into the binding interactions and electronic properties that contribute to antimicrobial potency. Structure–activity relationship (SAR) analysis highlighted the importance of substituent effects on biological activity. Overall, the findings demonstrate that benzimidazole remains a versatile and promising scaffold for antimicrobial drug discovery, and these newly synthesized derivatives represent valuable leads for further optimization against resistant bacterial strains.
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