【作者】 戴均贵； 曲润江； 邹建华； 陈晓光； 果德安；

【Author】 Jungui Dai1*, Yunjiang Qu1, Jian-Hua Zou1, Xiaoguang Chen1, Dean Guo2 1 Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 100050, Beijing 2 School of Pharmaceutical Sciences, Health Science Center, Peking University, 100083, Beijing

【机构】 中国医学科学院中国协和医科大学药物研究所； 北京大学医学部药学院；

【Abstract】 A “small taxane library” was established through chemo-enzymatic transformation of the taxanes derived from cell cultures of Taxus chinensis. The MDR reversal activity towards tumor and cytotoxicity of most these compounds were evaluated, and several derivatives exhibited powerful MDR reversal activity and low cytotoxicity. The structure-activity relationships of these compounds were also preliminarily summarized. The substrate-specificities of the two of most various important biotransformation reactions-C-7β and 9α hydroxylations, were investigated, the “structure-activity relationships” between substrates and enzymes were preliminarily concluded. The optimal tansformation conditions of the two hydroxylations were established, and the two hydroxylations were successfully combined. In addition, some key intermediates in the taxoid biosynthetic pathway were obtained. These results indicate that biotransformation is a powerful alternative to not only diversifying natural products, searching lead compounds and studying the SAR of the derivatives, also mimicking some steps in biosynthetic pathway of natural products and providing useful hints as to biosynthetic study.更多还原