QSAR study of natural estrogen-like isoflavonoids and diphenolics from Thai medicinal plants
QSAR study of natural estrogen-like isoflavonoids and diphenolics from Thai medicinal plants
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DOI：
10.1016/j.jmgm.2011.01.001
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发表时间：
2011-04-01
影响因子：
2.9
通讯作者：
Miertus, Stanislav
中科院分区：
文献类型：
--
作者：
De-Eknamkul, Wanchai;Umehara, Kaoru;Miertus, Stanislav
本文报道了两种泰国药用植物--小花黄檀Dalbergia parviflora R.（豆科植物）和射干（Belamcanda chinensis L.）（鸢尾科），传统上用于调节月经失调，已发现含有大量潜在的雌激素样化合物。在乳腺癌MCF-7和T47 D细胞增殖试验中，一组约55种分离的雌激素和双酚类化合物显示出广泛的雌激素活性。这组化合物进行了研究，通过计算技术，包括定量构效关系（QSAR）和分子建模。结果表明，所研究化合物的雌激素活性主要取决于骨架B环3'和5'端羟基的存在与否以及A环外端7位和B环4'端羟基间的原子间距。在采用配体-受体相互作用能量描述符的QSAR模型中，Cerius（2）虚拟筛选模块的LigScore评分函数（描述同时结合雌激素受体α和β（ER α和ER β）的受体亲和力）导致观察到的雌激素活性与计算的描述符之间的最佳相关性。考虑到与ER α和ER β的独立结合，没有产生统计学显著的QSAR模型。因此得出结论，化合物与ER α和ER β受体的同时和可能的竞争性相互作用，其中在上述位置上的羟基的存在下的雌激素和双酚类分子支架起主导作用，可能决定所考虑的植物化学物质的雌激素效力。(C)2011 Elsevier Inc. All rights reserved.
Two species of Thai medicinal plants, Dalbergia parviflora R. (Leguminosae) and Belamcanda chinensis L. (Iridaceae), used traditionally for the regulation of menstrual disorders, have been found to contain a large number of potential estrogen-like compounds. A set of some 55 isolated isoflavonoids and diphenolics showed a wide range of estrogen activity as determined in breast cancer MCF-7 and T47D cell proliferation assays. This set of compounds was studied by means of computational techniques including quantitative structure-activity relationships (QSAR) and molecular modeling. It was found that the estrogenic potencies of the studied compounds depend mainly upon the presence/absence of hydroxyl groups attached to 3' and 5' positions of B ring of the isoflavone scaffold and the inter-atomic distance between the hydroxyl groups attached to the outer terminal positions 7 of A ring and 4' of B ring. In a QSAR model employing ligand-receptor interaction energy descriptors, the LigScore scoring function of Cerius(2) virtual screening module, which describes the receptor affinities of simultaneous binding to estrogenic receptors alpha and beta (ER alpha and ER beta), led to the best correlation between the observed estrogenic activities and computed descriptors. Consideration of independent binding to ER alpha and ER beta did not result in statistically significant QSAR models. It was thus concluded that simultaneous and possibly competitive interaction of the compounds with the ER alpha and ER beta receptors, in which the presence of hydroxyl groups at the abovementioned positions of the isoflavonoids and diphenolics molecular scaffold plays a dominant role, may determine the estrogenic potency of the considered phytochemicals. (C) 2011 Elsevier Inc. All rights reserved.