A facile reaction to access novel structural sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents

[Display omitted] •Novel sulfonyl-hybridized imidazolyl ethanols were developed for the first time.•Compound 5f exerted better anti-MRSA activity than sulfathiazole and norfloxacin.•Compound 5f showed low tendency to induce drug resistance.•Compound 5f intercalated into DNA to form 5f-DNA complex.•Compound 5f could interact with dihydrofolate synthetase. A novel type of sulfonyl-hybridized imidazolyl ethanols as potential DNA-targeting antibacterial agents was constructed via the unique ring-opened reaction of oxiranes by imidazoles for the first time. Some developed target hybrids showed potential antimicrobial potency against the tested microbes. Especially, imidazole derivative 5f could strongly suppressed the growth of MRSA (MIC = 4 μg/mL), which was 2-fold and 16-fold more potent than the positive control sulfathiazole and norfloxacin. This compound exhibited quite low propensity to induce bacterial resistance. Antibacterial mechanism exploration indicated that compound 5f could embed in MRSA DNA to form steady 5f-DNA complex, which possibly hinder DNA replication to exert antimicrobial behavior. Molecular docking showed that molecule 5f could bind with dihydrofolate synthetase through hydrogen bonds. These results implied that imidazole derivative 5f could be served as a promising molecule for the exploration of novel antibacterial candidates.