短刺小克银汉霉与卷枝毛霉对昂丹司琼的转化

Transformation of Ondansetron by Cunninghamella blakesleana and Mucor circinelloides

采用微生物转化法考察11株放线菌及11株小型丝状真菌对昂丹司琼的转化能力,通过高效液相色谱-多级质谱(HPLC-MSn)检测转化产物。7株真菌可将昂丹司琼转化为7-羟基昂丹司琼和N-去甲基昂丹司琼,与文献中报道的人体内主要代谢产物相同,其中短刺小克银汉霉AS 3.153转化能力最强,在优化的转化系统中7-羟基昂丹司琼和N-去甲基昂丹司琼的产率分别达到57.80%和15.60%。此外,3株真菌和7株放线菌将昂丹司琼转化为1-羟基昂丹司琼,其中卷枝毛霉AS 3.3421转化能力最强,在优化的转化系统中,1-羟基异构体的总产率达43.10%。表明筛选出的2模型菌株对形成昂丹司琼的类哺乳动物代谢产物具有互补能力,在确定药物代谢产物种类及制备相应的对照品中具有应用价值,可作为药物代谢体外研究的有效辅助工具。

11 actinomycetes strains and 11 minor filamentous fungal strains were observed their capabilities on transformation of ondansetron adopting microbial-transformation method, and the transformant products were tested with HPLC-MSn. Ondansetron was transformed to 7-hydroxy ondansetron and N-demethyl ondansetron by 7 fungal strains and the product were the same as those major metabolites in human body as reported in references. Among them Cunninghamella blakesleana AS 3. 153 has the strongest capability of the transformation. Under the optimized transformation system （OTS） , its yield rate of 7-hydroxy ondansetron and N-demethyl ondansetron were 57.80% and 15.60% respectively. In addition, 3 fungal strains and 7 actinomycetes strains could transform ondansetron into 1-hydroxy ondansetron, among them Mucor circinelloides AS 3. 3421 has the strongest transformation capability. Under the OTS its total yield rate of isomer of 1-hydroxy ondansetron was 43.10%. These indicated that the screened model strains possess mutual compensation capability in forming mammalian metabolite of ondansetron, therefore they possess application value in confirming the kinds of metabolites and preparing corresponding control object, and can be used as effective supplementary tools of drug metabolism study in vitro.