Synthesis and biological evaluation of fluoroquinolones containing a pyridoxine derivatives moiety

被引：2

作者：

Shtyrlin, Nikita V. ^{[1
]}

Kayumov, Airat R. ^{[1
]}

Agafonova, Maria N. ^{[1
]}

Garipov, Marsel R. ^{[1
]}

Gatina, Alina E. ^{[1
]}

Pugachev, Mikhail V. ^{[1
]}

Bulatova, Elena S. ^{[1
]}

Grishaev, Denis Y. ^{[1
]}

Iksanova, Alfiya G. ^{[1
]}

Khaziev, Rail M. ^{[1
]}

Ganiev, Ilnur M. ^{[1
]}

Aimaletdinov, Aleksandr M. ^{[1
]}

Gnezdilov, Oleg I. ^{[2
]}

Shtyrlin, Yurii G. ^{[1
]}

机构：

[1] Kazan Volga Reg Fed Univ, Kremlyovskaya St 18, Kazan 420008, Russia

[2] Kazan E K Zavoisky Phys Tech Inst, Russian Acad Sci, Kazan Sci Ctr, Kazan EK Zavoisky Phys Tech Inst, 10-7 Ul Sibirskiy Trakt, Kazan 420029, Russia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 261卷

关键词：

Pyridoxine; Fluoroquinolone; Antibacterial activity; Toxicity; In vivo efficacy; ANTIBACTERIAL ACTIVITY; PHOSPHONIUM SALTS; INHIBITORS; QUINOLONE;

D O I：

10.1016/j.ejmech.2023.115798

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页数：18

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