Synthesis, molecular docking, and evaluation of antibacterial activity of 1,2,4-triazole-norfloxacin hybrids.

Abstract A series of 1,2,4-triazole-norfloxacin hybrids was designed, synthesized, and evaluated for in vitro antibacterial activity against common pathogens. All the newly synthesized compounds were characterized by Fourier-transform infrared spectrophotometry, proton and carbon nuclear magnetic resonance, and electrospray ionization-mass spectrometry. Representative compounds from each step of the synthesis were further characterized by X-ray crystallography. Many of the compounds synthesized exhibited antibacterial activity superior to that of norfloxacin toward both, gram-positive and gram-negative bacteria. The toxicity of the 1,2,4-triazole-norfloxacin hybrids toward bacterial cells was 32−512 times higher than that toward mouse fibroblast cells. Moreover, hemolysis was not observed at concentrations of 64 μg/mL, suggesting good biocompatibility. Molecular docking showed a least binding energy of −9.4 to −9.7 kcal/mol, and all compounds were predicted to show remarkable affinity for the bacterial topoisomerase IV.