短刺小克银汉霉AS 3.153菌株对丁咯地尔的代谢转化  

Microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153

作　　者：王薇[1] 杨亚楠[2] 马晓敏[1] 卜平[1] 孙璐[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]江苏恒瑞医药股份有限公司,江苏连云港222047

出　　处：《药学学报》2012年第7期934-940,共7页Acta Pharmaceutica Sinica

摘　　要：建立能够模拟丁咯地尔在哺乳动物体内代谢的微生物模型,研究丁咯地尔在微生物体内的转化途径,并应用该模型制备代谢产物。菌株筛选实验中考察了4种小克银汉霉对丁咯地尔的转化能力,确定最佳菌株为短刺小克银汉霉AS 3.153;然后针对该菌株进行转化条件(培养基初始pH、底物浓度和转化时间)优化,建立微生物模型。应用LC-MSn法对转化样品进行分析,共检测到3种代谢产物,其中2种为首次发现的丁咯地尔代谢产物,进一步采用半制备液相色谱法制备获得对位-O-去甲基丁咯地尔和12-C-氧化丁咯地尔。哺乳动物对比实验表明,短刺小克银汉霉AS 3.153对丁咯地尔的代谢情况与人和比格犬类似,而与大鼠差异较大。The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153 was studied, as well as a microbial model which can be used to mimic metabolism of buflomedil in mammal was established. Experiments were conducted to screen the capabilities of four strains of Cunninghamella species to transform buflomedil, in which C. blakesleana AS 3.153 was selected for a preparative biotransformation. Furthermore, the microbial model was established based on the transformation condition optimization. The parent drug and its metabolites produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass spectrometry method and three metabolites were identified while two of them were new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12-C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the comparison between different species, the microbial transformation of buflomedil by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in human and Beagle dog than that in rat.

关 键 词：丁咯地尔 微生物转化 短刺小克银汉霉AS 3.153 

分 类 号：R969[医药卫生—药理学]