【摘要】 选用短刺小克银汉霉菌AS 3.15 3对苯丙哌林进行微生物转化研究 .根据液相色谱和质谱数据推测 ,转化产物分别为苯丙哌林单羟基化物 (约6 5 % ) ,苯丙哌林双羟基化物和苯丙哌林单羟基化物的硫酸酯结合物 .发现苯丙哌林的微生物转化与其在人体内的药物代谢有很多相似之处 ,转化菌株能产生人体Ⅰ相代谢产物和部分Ⅱ相代谢产物 .考察了影响单羟基转化产物形成的因素 ,发现以pH 6 .5 ,底物浓度 0 .0 5 % ,转化反应持续 72h等条件较为适宜 .通过半制备高效液相色谱法分离出两种主要转化产物 ,经核磁共振光谱分析确证其结构分别为 4 羟基苯丙哌林和 4′ 羟基苯丙哌林 .结果表明 ,微生物转化模型是研究苯丙哌林代谢适宜的体外模型更多还原

【Abstract】 Studies on biotransformation of benproperine by Cunninghamella blakesleana AS 3.153 were conducted. The observed transformation products were metabolites of mono hydroxylation (approx.65%), di hydroxylation and sulfate conjugation of mono hydroxylated derivatives of benproperine by LC/MS n data. Compared with data of metabolites in urine of healthy male volunteers, similarities were found between microorganism and humans in the transformation of benproperine. The transformation organism produced phase Ⅰ and a part of phase Ⅱ metabolites in humans. Influences of the mono hydroxylation were investigated, and the optimized conditions were pH 6.5, 0.05% of substrate concentration, and 72 h of incubation. Semi preparative HPLC was used to isolate two major transformation products, and their structures were then identified as 4 hydroxybenproperine and 4′ hydroxybenproperine by NMR, respectively. Microbial model of transformation is shown to be a suitable in vitro model for benproperine metabolism.更多还原