氟喹诺酮C-3酰腙的合成与抗菌活性  

Synthesis and Antibacterial Activity of Fluoroquinolone C-3 Acylhydrazones

作　　者：胡国强[1] 张忠泉[1] 王新[1] 张智强[1] 张天栋[1] 谢松强[1] 黄文龙[2] 

机构地区：[1]河南大学化学与生物学研究所,河南开封475004 [2]中国药科大学,南京210009

出　　处：《中国药学杂志》2010年第11期867-870,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(20872028)

摘　　要：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.aureusATCC29213)、大肠埃希氏菌(E.coliATCC25922)、铜绿假单孢菌(P.aeruginosaATCC2785)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>128μg.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>8μg.mL-1),尤其是香草醛环丙酰腙(5d)对S.aureus及E.coli的MIC≥0.5μg.mL-1,对P.aeruginosa的MIC≥1.0μg.mL-1,其抗菌活性与对照环丙沙星相当(MIC≥0.5μg.mL-1),而优于氧氟沙星(MIC≥2.0μg.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。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.

关 键 词：氟喹诺酮 酰腙 抗菌活性 

分 类 号：R914.5[医药卫生—药物化学]