Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?
Structural requirements for the interaction of combretastatins with tubulin: how important is the trimethoxy unit?
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DOI：
10.1039/b306878a
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发表时间：
2003-01-01
影响因子：
3.2
通讯作者：
McGown, AT
中科院分区：
文献类型：
--
作者：
Gaukroger, K;Hadfield, JA;McGown, AT
已经合成了一系列在环A上具有三甲氧基单元和其他取代基的考布他汀，并测试了其细胞毒性和与蛋白质微管蛋白相互作用的能力。所有以前的研究表明，三甲氧基单元是必不可少的相互作用与微管蛋白。本文的研究表明，具有三甲氧基以外的官能团的分子也可以与微管蛋白相互作用。重要的是，三甲基取代的试剂52a显示出降低的细胞毒性，但其抑制微管蛋白组装的能力的效力增加。
A series of combretastatins possessing both a trimethoxy unit and other substituents on ring A has been synthesised and tested for cytotoxicity and their ability to interact with the protein tubulin. All previous studies have indicated that the trimethoxy unit is essential for interaction with tubulin. The studies herein show that molecules possessing functionalities other than trimethoxy can also interact with tubulin. Importantly a trimethyl substituted agent 52a has shown reduced cytotoxicity, but increased potency in its ability to inhibit the assembly of tubulin.