1. Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety.
- Author
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Shtyrlin, Nikita V., Kayumov, Airat R., Agafonova, Maria N., Garipov, Marsel R., Gatina, Alina E., Pugachev, Mikhail V., Bulatova, Elena S., Grishaev, Denis Y., Iksanova, Alfiya G., Khaziev, Rail M., Ganiev, Ilnur M., Aimaletdinov, Aleksandr M., Gnezdilov, Oleg I., and Shtyrlin, Yurii G.
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BIOSYNTHESIS , *VITAMIN B6 , *ANTIBACTERIAL agents , *LEAD compounds , *MOIETIES (Chemistry) , *THIOUREA , *FLUOROQUINOLONES , *OXAZOLIDINONES - 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 (LD 50 > 2000 mg/kg, oral) and rats (LD 50 > 2000 mg/kg, oral). Compound 28 was more toxic (LD 50 = 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. [Display omitted] • Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety • The compounds exhibited in vitro promising antibacterial activity against Gram-positive and Gram-negative bacterial strains. • Lead compound 7 is non-toxic in vivo on mice (LD 50 > 2000 mg/kg, oral) and rats (LD 50 > 2000 mg/kg, oral) and showed greater in vivo efficacy compared to ciprofloxacin in a murine model of staphylococcal sepsis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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