Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety

  • Eur J Med Chem. 2023 Sep 7:261:115798. doi: 10.1016/j.ejmech.2023.115798.
Nikita V Shtyrlin  1 ,  Airat R Kayumov  2 ,  Maria N Agafonova  2 ,  Marsel R Garipov  2 ,  Alina E Gatina  2 ,  Mikhail V Pugachev  2 ,  Elena S Bulatova  2 ,  Denis Y Grishaev  2 ,  Alfiya G Iksanova  2 ,  Rail M Khaziev  2 ,  Ilnur M Ganiev  2 ,  Aleksandr M Aimaletdinov  2 ,  Oleg I Gnezdilov  3 ,  Yurii G Shtyrlin  4
Affiliations
  • 1. Kazan (Volga region) Federal University, Kremlyovskaya St. 18, Kazan, 420008, Russian Federation. Electronic address: [email protected].
  • 2. Kazan (Volga region) Federal University, Kremlyovskaya St. 18, Kazan, 420008, Russian Federation.
  • 3. Kazan E. K. Zavoisky Physical-Technical Institute, Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences", 10/7 ul. Sibirskiy trakt, Kazan, 420029, Russian Federation.
  • 4. Kazan (Volga region) Federal University, Kremlyovskaya St. 18, Kazan, 420008, Russian Federation. Electronic address: [email protected].
PMID: 37729692 DOI: 10.1016/j.ejmech.2023.115798
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.
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