Effects of 7-O Substitutions on Estrogenic and Anti-Estrogenic Activities of Daidzein Analogues in MCF-7 Breast Cancer Cells

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• 作者：Quan Jiang ; Florastina Payton-Stewart ; Steven Elliott ; Jennifer Driver ; Lyndsay V. Rhodes ; Qiang Zhang ; Shilong Zheng ; Deepak Bhatnagar ; Stephen M. Boue ; Bridgette M. Collins-Burow ; Jayalakshmi Sridha
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：August 26, 2010
• 年：2010
• 卷：53
• 期：16
• 页码：6153-6163
• 全文大小：1083K
• 年卷期：v.53,no.16(August 26, 2010)
• ISSN：1520-4804

文摘

Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7-hydroxyl hydrogen. To test the effect of such structural modifications on the hormonal activities of the resulting compounds, a series of daidzein analogues have been designed and synthesized. When MCF-7 cells were treated with the analogues, those resulting from hydrogen substitution by isopropyl (3d), isobutyl (3f), cyclopentyl (3g), and pyrano- (2) inhibited cell proliferation, estrogen-induced transcriptional activity, and estrogen receptor (ER) regulated progesterone receptor (PgR) gene expression. However, methyl (3a) and ethyl (3b) substitutions of the hydroxyl proton only led to moderate reduction of the estrogenic activities. These results demonstrated the structural requirements for the transformation of daidzein from an ER agonist to an antagonist. The most effective analogue, 2, was found to reduce in vivo estrogen stimulated MCF-7 cell tumorigenesis using a xenograft mouse model.