Synthesis, Characterization, and Bioactivity Investigation of Novel Benzimidazole Derivatives as Potential Antibacterial and Antifungal Agents

Abstract

A series of benzimidazole derivatives 6a–j was designed and synthesized via the condensation of the corresponding o-phenylenediamine intermediates with formic acid. Antibacterial activity was evaluated in vitro using the agar well diffusion method against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella pneumoniae, with nitrofurantoin (300 µg/mL) as the positive control. Antifungal screening was performed against Aspergillus flavus, Penicillium duclauxii, and P. italicum at 20 and 50 µg/mL, with Amphotericin B as the reference drug at the same concentrations. Most compounds exhibited moderate to good antimicrobial activity. MIC determination identified 6h as the most active antibacterial agent (MIC = 5.0 µg/mL). The SEM analysis of bacteria treated with 6h revealed marked morphological damage, including cell deformation and membrane disruption, supporting a bactericidal mode of action. Collectively, these results highlight benzimidazole derivatives as promising scaffolds for the development of broad-spectrum antibacterial and antifungal agents.