Structure-activity relationships of terpendole E and its natural derivatives.
Structure-activity relationships of terpendole E and its natural derivatives.
复制标题
萜烯E及其天然衍生物的构效关系。
DOI：
10.1002/slct.201602015
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发表时间：
2017
期刊：
影响因子：
2.1
通讯作者：
Usui T
中科院分区：
文献类型：
--
作者：
Nagumo Y;Hayashi T;Hirota H;Aono H;Kawatani M;Osada H;Usui T
Terpendole E（TerE）是第一个抑制有丝分裂驱动蛋白Eg 5（驱动蛋白纺锤体蛋白）的天然产物。最近，TerE被认为具有与其他L5环结合型Eg 5抑制剂不同的结合位点和/或抑制机制。在这里，我们报告了天然TerE衍生物的结构活性关系（SAR），包括两个以前没有报道的化合物。我们的SAR结果表明，雀稗样吲哚-二萜骨架对Eg 5抑制是重要的，并且除了11位之外的进一步氧化和进一步的异戊二烯化都会降低Eg 5抑制活性。
Terpendole E (TerE) is the first natural product that inhibits mitotic kinesin Eg5 (kinesin spindle protein). Recently, TerE is suggested to have a different binding site and/or inhibitory mechanism than other L5 loop‐binding type Eg5 inhibitors. Here, we report the structure‐activity relationships (SARs) of natural TerE derivatives, including two compounds not reported before. Our SAR results indicated that the paspaline‐like indole‐diterpene skeleton is important for Eg5 inhibition, and that both further oxidation except for 11‐position and further prenylation decreases the Eg5 inhibitory activity.