The Biotransformation Research Of Methyl Protodioscin

MPD is a furostanol saponin isolated from the anti-cancer traditional Chinese medicine Dioscorea hypoglauca , which exhibits obvious cytotoxic activity on human tumor cell in vitro by National Cancer Institute (NCI) Its chemical structure has been established by chemical evidences in combination with spectral data.The aim of this study was to investigate biotransformation of MPD in microbe and to study the metabolites in rats to characterize not only the evaluation of the availability value and security of drugs, but also some useful hints for the decision of the therapeutic project.In the research of microbial transformation of MPD, 29 fungi were screened and two of them (Aspergillus niger and Penicillium janthinellum ) having good ability of conversion were selected for further research. Various kinds of modern chromatographic methods were applied for the isolation of biotransformation products, such as partitioned with different solvents, Diaion HP-20, open and MPLC silica gel,ODS, Rp-HPLC et al.The microbial biotransformation of MPD by Aspergillus niger AS3.1858, yielded nine products and seven of them were elucidated. Ten products were afforded and identified from the potato medium in the microbial biotransformation of MPD by Penicillium janthinellum AS3.510. Most of the bioconversion products are steroidal saponins and pregnane glycoside. It is the first time to find that the bioconversion of steroid to pregnenolone could be done by fungi only, which must be transformed combining with chemical transformation procedures in the reported literatures. This finding enriched the types of bioconversion reaction and provided a new way for the production of androstedione. A new furostanol saponin was found from the potato medium in the biotransformation of MPD by Penicillium janthinellum AS3.510. The proposed biotransformation pathways of MPD were deduced respectively.In the study of biotransformation of MPD in rats, two different administration approaches were performed respectively, including intragastrical administration and intravenous injection. Biological samples were accumulated and the metabolites in urine and feces were isolated using various kinds of modern chromatographic methods.Biotransformation of MPD in rats through intragastrical administration yielded ten products. Eighteen metabolites were isolated and fourteen of them were identified in the biotransformation...