手机知网 App
24小时专家级知识服务
打 开
手机知网|搜索

紫杉烷类化合物的化学酶法转化及其肿瘤多药耐药逆转活性评价

戴均贵;曲润江;邹建华;陈晓光;果德安

  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.……