Benzimidazole and Imidazole Hydrazone Derivatives as Promising Antibacterial Scaffolds: Synthesis, Biological Evaluation, and Safety Assessment

ABSTRACT

A series of new hydrazone derivatives containing imidazole and benzimidazole cores were designed, synthesized, and evaluated for antimicrobial activity, biocompatibility, and biotoxicity. The target compounds were prepared through N‐alkylation, hydrazide formation, and subsequent condensation with selected aromatic aldehydes. Their structures were characterized by FTIR, ¹ H NMR, ¹³ C NMR, and mass spectrometry. The NMR spectra revealed the presence of cis/trans amide conformers arising from restricted rotation about the amide C─N bond in solution. Antibacterial activity was evaluated against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 using the minimum inhibitory concentration (MIC) method, while biocompatibility was assessed by a human red blood cell hemolysis assay. In vivo studies examined antioxidant status and histopathological effects in liver and kidney tissues. Compound 8 exhibited the highest antibacterial activity, with MIC values of 15.625 and 62.5 µg/mL against S. aureus and E. coli , respectively. In contrast, compound 6 showed superior biocompatibility, lower hemolytic activity, minimal toxicity, and near‐normal GSH, GPx, and CAT levels. Histopathological examination further demonstrated preservation of liver and kidney architecture following treatment with compound 6 .