卡德沙星代谢物的合成、结构确证及其体外抗菌活性

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

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。

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.