Antimicrobial effects of new tetrahydrofurans

The increasing challenge of antimicrobial resistance (AMR) necessitates abrupt attention to discovering a new class of antimicrobials. In this study, we made efforts to prepare some fluoro-phenyl tetrahydrofurans-based DNA gyrase inhibitors as anti-microbial agents. To obtain the title compounds difluoro phenyl tetrahydrofurans (1-12), we used fluorophenyl-tetrahydrofuran and methyl benzenesulfonate to react with isoxazole derivatives and heterocyclic compounds bearing secondary amines in the presence of dimethylformamide (DMF) and sodium hydride (NaH) or potassium carbonate (K₂CO₃). The compounds were obtained in moderate to excellent yields and were characterized with FTIR, HRMS, NMR, etc. Among all compounds (1-12), compounds 1, 2, 11, and 12 were active against various Gram-positive and Gram-negative bacteria at a low concentration (MIC ranged between 1.25 and 9.75 μg/mL) and displayed low toxicity towards mammalian cells. We testified the in vitro DNA gyrase inhibitory potential for these compounds. A molecular docking study and an ADMET assessment study were carried out to understand the mode of interaction of ligand-DNA gyrase. In conclusion, we screened the compounds 1, 2, 11, and 12 for further clinical and pre-clinical studies.