Abstract

This study addresses the growing challenge of antimicrobial resistance by synthesizing and evaluating a novel hydroxylamine derivative of tinidazole (M4). Tinidazole, a widely used nitroimidazole, has limitations associated with resistance mechanisms and potential genotoxicity. In this study, M4 was successfully synthesized through the selective reduction of the 5-nitro group of tinidazole, and its structure was thoroughly characterized using FT-IR, mass spectrometry, and NMR spectroscopy. In vitro biological evaluation demonstrated that M4 exhibited superior antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Klebsiella pneumoniae) bacteria compared with the parent compound, tinidazole. This enhanced efficacy is attributed to the preformed hydroxylamine structure of M4, which bypasses the enzymatic reduction step required for the activation of tinidazole, thereby overcoming common resistance mechanisms. These findings highlight the potential of M4 as a more potent antimicrobial agent and provide a foundation for further structure–activity relationship investigations.