氟喹诺酮C-3酰腙的合成与抗菌活性

 目的 评价氟喹诺酮C-3位羧基被酰腙替代对其抗菌活性影响，为进一步扩大结构修饰提供新的途径。方法 第三代氟喹诺酮类药物氧氟沙星及环丙沙星为起始原料，经肼解成其相应的酰肼，然后分别与芳香醛进行缩合得系列C-3酰腙目标化合物。用琼脂稀释法研究了目标化合物体外对标准菌株金黄色葡萄球菌(S. aureus ATCC29213)、大肠埃希氏菌(E. coli ATCC25922)、铜绿假单孢菌(P. aeruginosa ATCC2785)的生长抑制活性。结果 合成了12个新的目标酰腙化合物，体外活性结果表明，氧氟沙星类酰腙化合物表现出较弱的体外抗菌活性(其MIC＞128 μg·mL^-1)，而多数环丙沙星类酰腙化合物却表现出较强的体外抗菌活性(其MIC＞8 μg·mL^-1)，尤其是香草醛环丙酰腙(5d)对S. aureus及E. coli的MIC≥0.5 μg·mL^-1，对P. aeruginosa的MIC≥1.0 μg·mL^-1，其抗菌活性与对照环丙沙星相当(MIC≥0.5 μg·mL^-1)，而优于氧氟沙星(MIC≥2.0 μg·mL^-1)。结论 抗菌药氟喹诺酮C-3位羧基被其他取代基替代值得进一步研究。

Synthesis and Antibacterial Activity of Fluoroquinolone C-3 Acylhydrazones

OBJECTIVE To evaluate an influence for the placement of C-3 fluoro quinolone carboxylic group with acylhydrazone on the antibacterial activity. METHODS A series of C-3 acylhydrazones derived ciprofloxacin and ofloxacin were synthesized by a condensation the corresponding C-3 hydrazides with aromatic aldehydes， and the in vitro antibacterial activities of newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. RESULTS Twelve title compunds were synthesized， and their structures were characterized by their spectral data. Some ciprofloxacin derivatives showed potential antibacterial activity but ofloxacin derivatives had poor activity. CONCLUSION The C-3 carboxyl-based substituted antibacterial fluoroquinolones are valuable for further study.