Synthesis, biological activity and tubulin binding poses of 1-deoxy-9-(R)-dihydrotaxane analogs.
Synthesis, biological activity and tubulin binding poses of 1-deoxy-9-(R)-dihydrotaxane analogs.
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DOI：
10.1016/j.bmcl.2008.12.091
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发表时间：
2009-02
影响因子：
2.7
通讯作者：
Tian-Hai Yuan;Yi Jiang;Xiao‐hong Wang;Dian-Long Wang;Abhijit Bannerjee;S. Bane;J. Snyder;Haixia Lin
中科院分区：
文献类型：
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作者：
Tian-Hai Yuan;Yi Jiang;Xiao‐hong Wang;Dian-Long Wang;Abhijit Bannerjee;S. Bane;J. Snyder;Haixia Lin
从红豆杉中分离得到1-脱氧巴accatin VI半合成1-脱氧-9α-二氢紫杉烷类似物9和10，并对其细胞毒活性进行了测试。紫杉醇9的细胞毒性比紫杉醇低10倍，而紫杉醇10的活性相同。在微管蛋白聚合试验（ed50值）中，10的效果比紫杉醇低4倍，但比9好3倍。这些观察结果可以通过分析相应的紫杉烷/β-微管蛋白复合物来解释。
1-Deoxy-9α-dihydrotaxane analogs 9 and 10 were semi-synthesized from 1-deoxybaccatin VI, isolated from Taxus mairei, and tested for cytotoxic activity. Taxane 9 is 10-fold less cytotoxic than paclitaxel, while 10 is equally active. In the tubulin polymerization assay (ED50values), 10 is 4-fold less effective than paclitaxel, but 3-fold superior to 9. These observations can be explained by analysis of the corresponding taxane/β-tubulin complexes.