title: Chemo-enzymatic transformation of taxanes and their reversal activity towards MDR tumor cells.
abstract: Over 200 derivatives have been obtained through chemo-enzymatic transformation of the taxanes derived from cell cultures of Taxus chinensis. The reversal activity towards MDR tumor cells and cyto-toxicity of most these compounds were evaluated, and several derivatives exhibited powerful MDR reversal activity. The substrate-specificities of the two most important biotransformation reactions-C-7beta and 9alpha hydroxylations, were investigated and preliminarily concluded. In addition, some key intermediates in hypothetically biosynthetic pathway of taxoid were obtained. These results indicate that biotransformation combined with chemical transformation is a powerful approach to structural diversification of natural products, lead compound discovery and the study on the structure activity relationships of the derivatives. Moreover, biotransformation may mimic some steps in biosynthetic pathway of natural products and provide useful hints as to their biogenetic study.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College (Key Laboratory of Biosynthesis of Natural Drugs, Ministry of Public Health & Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education), 1 Xian Nong Tan Street, Beijing 100050, PR China. jgdai@imm.ac.cn
authors.forename: Jungui
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D020946:Taxus / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D001688:Biological Products; D043823:Taxoids