论文部分内容阅读
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。
To establish a microbial model that can simulate the metabolism of buflomedil in mammals, study the conversion of buflomedil in the microorganism, and use this model to prepare the metabolites. In the screening experiment, the transformation ability of four species of Cryptopodiaceae to buflomedil was investigated, and the best strain was identified as Cryptocaryon burgdorferi AS 3.153. Then, the transformation conditions (initial pH of medium, substrate Concentration and conversion time) to establish a microbial model. The LC-MSn method was used to analyze the transformed samples. Three metabolites were detected, of which two were the first detected buflomedil metabolites, and further prepared by semi-preparative liquid chromatography Buprenorphine and 12-C-buflomedil. Mammalian contrast experiments showed that the metabolism of Bufo bufo gargarizans AS 3.153 to buflomedil was similar to that in humans and beagle dogs, but significantly different from that in rats.