title: Biotransformation of 20(S)-protopanaxatriol by Mucor spinosus and the cytotoxic structure activity relationships of the transformed products.
abstract: Biotransformation of 20(S)-protopanaxatriol (1) by the fungus Mucor spinosus AS 3.3450 gave 10 metabolites (2-10), of which 2-5 were previously known. On the basis of NMR and MS analyses, structures 6-10 were established as 12-oxo-23beta-hydroxyl-20(S)-protopanaxatriol (6), 20S,24R-epoxy-dammaran-3beta,6alpha,25-triol-12-one (7), 29-hydroxyl-20(S)-protopanaxatriol (8a), 12-oxo-11beta-hydroxyl-20(S)-protopanaxatriol (8b), 28-hydroxyl-20(S)-protopanaxatriol (9) and 12-oxo-20(S)-protopanaxatriol (10). The biotransformation kinetics of 1 has been investigated and a possible biotransformation pathway proposed. The in vitro cytotoxic activities of metabolites against three human cancer cell lines were determined by the MTT method; compounds 8a, 9 and 10 had more potent inhibitory effects against HL-60 cell line than the substrate.
authors.affiliation: Division of Pharmacognostical Biotechnology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Guo
authors.forename: Yin
authors.initials: Y
authors.lastname: Tian
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001711:Biotransformation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009089:Mucor / Q000378:metabolism*; D012502:Sapogenins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012502:Sapogenins; D014315:Triterpenes; C081552:protopanaxatriol