Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety

Abstract

We report herein the design, synthesis and biological evaluation of series of 7-substituted fluoroquinolones with pyridoxine derivatives. In vitro screening of antibacterial activity and toxicity of 39 synthesized fluoroquinolones defined compounds 7 and 28 as lead compounds for further investigations. On various clinical isolates lead compounds 7 and 28 exhibited antibacterial activity comparable with reference fluoroqinolones. Mutagenic effects haven't been observed for these compounds in SOS-chromotest. Compound 7 are non-toxic in vivo on mice (LD₅₀ > 2000 mg/kg, oral) and rats (LD₅₀ > 2000 mg/kg, oral). Compound 28 was more toxic (LD₅₀ = 474 mg/kg, oral, mice). Moreover compound 7 showed greater in vivo efficacy compared to ciprofloxacin in a murine model of staphylococcal sepsis. Taken together the described active compound are promising candidate for preclinical trials.

Keywords: Antibacterial activity; Fluoroquinolone; In vivo efficacy; Pyridoxine; Toxicity.