卡德沙星代谢物的合成、结构确证及其体外抗菌活性

目的:合成并确证卡德沙星两种代谢产物,初步研究其抗菌活性。方法:大鼠灌胃卡德沙星(9mg/kg)后,通过LC-MS分析,在胆汁和尿液中发现有m/z385.90的成分(M-1),在尿液中发现有m/z329.1的成分(M-2)。参考类似物的代谢方式,推测其结构分别为1-环丙基-6-氟-8-二氟甲氧基-1,4-二氢-7-(2-氨基-丙胺基)-4-氧代-3-喹啉羧酸和1-环丙基-6-氟-8-二氟甲氧基-1,4-二氢-7-氨基-4-氧代-3-喹啉羧酸。化学合成这两种物质,与卡德沙星的代谢产物进行对比,并研究体外抗菌活性。结果与结论:本文对卡德沙星代谢物的结构推断正确,它们的体外抗菌活性很弱。M-1和M-2均未见文献报道。

Synthesis, structure confirmation of cadrofloxacin metabolites and its antiboacterial activity in vitro

Aim:To synthesize two compounds and to confirm whether they have the same chemical structures as those of the two cadrofloxacin metabolites found in a pilot study.Methods:Following ig administration of cadrofloxacin(9 mg/kg) to rat,two components were found by LC-MS,one component named M-1 of m/z 385.9 in bile and urine,the other named M-2 of m/z 329.1 in urine.According to the chemical structures we conjectured that M-1 and M-2 were 1-cyclopropyl-6-fluoro-8-difluoromethoxy-1,4-dihydro-7-2-amino-propylamino]-4-oxo-3-quinolinecarboxylic acid and 1-cyclopropyl-6-fluoro-8-difluoromethoxy-1,4-dihydro-7-amion-4-oxo-3-quinolinecarboxylic acid respectively.Two compounds were synthesized and compared with the cadrofloxacin metabolites in vivo,then the in vitro activities of the synthesis compounds were compared with cadrofloxacin lactate.Results and Conclusion:Chemical structures of the two cadrofloxacin metabolites were confirmed.They showed poor antibacterial activities in vitro.M-1 and M-2 were reported for the first time.