Synthesis and biological evaluation of p-carborane bisphenols and their derivatives: Structure-activity relationship for estrogenic activity
Synthesis and biological evaluation of p-carborane bisphenols and their derivatives: Structure-activity relationship for estrogenic activity
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DOI：
10.1016/j.bmc.2008.12.044
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Endo, Yasuyuki
中科院分区：
文献类型：
--
作者：
Ogawa, Takumi;Ohta, Kiminori;Endo, Yasuyuki
制备对碳硼烷双酚及其衍生物，并评价其与雌激素受体α的结合亲和力。用MCF-7细胞系进行转录活性测定和细胞增殖活性测定。在反式激活试验中，1，12-双（4-羟基苯基）-1，12-二碳-闭合-十二硼烷4a显示出强的雌激素活性，接近17 β-雌二醇。异构体5a和6a的活性受到其中一个羟基位置变化的显著影响; 6a（一个环中的邻位-OH）的效力比4a低约1000倍。用烷基修饰该羟基降低了所有异构体的雌激素活性。化合物4a还显示出有效的MCF-7细胞增殖增强活性。(C)2008爱思唯尔有限公司保留所有权利。
p-Carborane bisphenols and their derivatives were prepared and evaluated for binding affinity to estrogen receptor alpha. Their estrogenic activity was evaluated by means of transcriptional assay and cell proliferation assay using MCF-7 cell lines. 1,12-Bis(4-hydroxyphenyl)-1,12-dicarba-closo-dodecaborane 4a showed potent estrogenic activity, approaching that of 17 beta-estradiol, in transactivation assay. The activity of isomers 5a and 6a was drastically affected by the change in the position of one of the hydroxyl groups; 6a (ortho-OH in one ring) was about 1000 times less potent than 4a. Modification of this hydroxyl group with alkyl groups decreased the estrogenic activity in all isomers. Compound 4a also showed potent MCF-7 cell proliferation-enhancing activity. (C) 2008 Elsevier Ltd. All rights reserved.