Conformational analysis of rhazinilam and three-dimensional quantitative structure-activity relationships of rhazinilam analogues
Conformational analysis of rhazinilam and three-dimensional quantitative structure-activity relationships of rhazinilam analogues
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DOI：
10.1016/j.bmcl.2004.12.027
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发表时间：
2005-02-15
影响因子：
2.7
通讯作者：
Kobayashi, J
中科院分区：
文献类型：
--
作者：
Morita, H;Awang, K;Kobayashi, J
采用比较分子场分析（CoMFA）方法，研究了从夹竹桃科植物Rhazya stricta中分离得到的具有微管解聚活性的生物碱rhazinilam（1）及其衍生物的三维定量构效关系。为了更好地了解1的构象与抗微管蛋白活性之间的相关性，根据1在溶液中的NMR数据，分析了1在溶液中的最可能最小能量构象。结果表明这些生物碱的抗微管蛋白活性与调节其生物活性的空间和静电因素之间存在相关性，并解释了1的有效活性与整体构象的适当关系。(C)2004爱思唯尔有限公司保留所有权利。
3D QSAR of rhazinilam (1), an alkaloid isolated from Rhazya stricta (Apocynaceae) with an activity involving disassembly of microtubules and its derivatives was investigated by using the comparative molecular field analysis (CoMFA). In an effort to get a better understanding of the correlation between conformation and antitubulin activity of 1, most probable minimum energy conformation in solution of 1 was analyzed on the basis of NMR data of 1 in solution. The results indicated a correlation between the antitubulin activity of these alkaloids and the steric and electrostatic factors, which modulate their biological activity, and accounted for the potent activities of 1 with suitable relationship for the overall conformation. (C) 2004 Elsevier Ltd. All rights reserved.