Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens
Estrogenic and antiandrogenic activities of 17 benzophenone derivatives used as UV stabilizers and sunscreens
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DOI：
10.1016/j.taap.2004.07.005
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发表时间：
2005-02-15
影响因子：
3.8
通讯作者：
Ohta, S
中科院分区：
文献类型：
--
作者：
Suzuki, T;Kitamura, S;Ohta, S
本文用荧光反应报告基因分析法比较了紫外光稳定剂二苯甲酮及其16种衍生物的雌激素和抗雄激素活性。羟基化二苯甲酮类化合物对人乳腺癌细胞MCF-7具有雌激素样活性，但活性差异较大。观察到2，4，4 '-三羟基二苯甲酮（2.4，4'-triOH-BP）的活性最高，其次是2，3 '，4，4'-四羟基二苯甲酮、4，4 '-二羟基二苯甲酮、2，2'，4，4 '-四羟基二苯甲酮、4-羟基二苯甲酮和2，4-二羟基二苯甲酮。二苯甲酮本身在测定中显示出很小的活性。与此相反，二苯甲酮和一些相关化合物对大鼠成纤维细胞系NIH 3 T3的双氢睾酮的雄激素活性显示出显着的抑制作用。2，4，4 ′-triOH-BP的活性最高，其次是2，3 ′，4，4 ′-四羟基二苯甲酮、2，2 ′，4，4 ′-四羟基二苯甲酮、3-羟基二苯甲酮和2，2 ′-二羟基二苯甲酮。然而，2，3，4，4 '-四羟基二苯甲酮和2，3，4-三羟基二苯甲酮显示出很小的活性。2，4-二羟基二苯甲酮、2，4，4 '-triOH-BP和二苯甲酮在去卵巢大鼠子宫增重试验中呈阳性反应，2，4，4'-triOH-BP在去势大鼠Hershberger试验中呈阳性反应。这些结果表明，在二苯甲酮衍生物的苯环上的4-羟基基团对于高激素活性是必不可少的，并且其他羟基基团的存在显著改变这些活性。(C)2004年爱思唯尔公司All rights reserved.
Estrogenic and antiandrogenic activities of benzophenone and 16 of its derivatives, which are used as UV stabilizers, were comparatively examined with hormone-responsive reporter assay in various cell lines. Hydroxylated benzophenones exhibited estrogenic activity in human breast cancer cell line MCF-7, but their activities varied markedly. The highest activity was observed with 2,4,4'-trihydroxybenzophenone (2.4.4'-triOH-BP), followed by 2,3',4,4'-tetrahydroxybenzophenone, 4,4'-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 4-hydroxybenzophenone and 2,4-dihydroxybenzophenone. Benzophenone itself showed little activity in the assay. In contrast, benzophenone and some related compounds showed significant inhibitory effects on the androgenic activity of dihydrotestosterone in rat fibroblast cell line NIH3T3. The highest activity was observed with 2,4,4'-triOH-BP, followed by 2,3',4,4'-tetrahydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 3-hydroxybenzophenone and 2,2'-dihydroxybenzophenone. However, 2,3,4,4'-tetrahydroxybenzophenone and 2,3,4-trihydroxybenzophenone showed little activity. 2,4-Dihydroxybenzophenone, 2,4,4'-triOH-BP and benzophenone gave positive responses in uterotrophic assay using ovariectomized rats, and 2,4,4'-triOH-BP was positive in the Hershberger assay using castrated rats. These results suggest that a 4-hydroxyl group on the phenyl ring of benzophenone derivatives is essential for high hormonal activities, and the presence of other hydroxyl groups markedly alters these activities. (C) 2004 Elsevier Inc. All rights reserved.