科研之友
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摘要
Context: Mansonone G and mansorin A are major bioactive constituents from Mansonia gagei Drumm (Sterculiaceae) wood, and their mild anti-estrogenic activity was reported previously by the authors. %26lt;br%26gt;Objective: In order to increase the potency of their anti-estrogenic effect and to clarify their binding way to estrogen receptor on a molecular level, several derivatives of both compounds will be prepared and a docking study of the original compounds and their derivatives on estrogen receptor alpha (ER alpha) was carried out. %26lt;br%26gt;Materials and methods: The original compounds were isolated from the heartwood of M. gagei. Nine alkyl derivatives were prepared by acetylation, methylation, or adding a basic side chain to the free hydroxyl group of both compounds. The estrogenic/ anti-estrogenic activities of the derivatives compared to the original compounds were carried out using ER alpha competitive binding screen and yeast two-hybrid assay expressing ER alpha and ER beta using concentrations ranging from 10 to 100 mu M. %26lt;br%26gt;Results: Acetyl mansonone G showed a 10-fold increase in its binding ability to ER alpha compared to mansonone G with an IC50 630 mu M. Similarly, methyl mansonone G and acetyl mansonone G showed 50% and 35% inhibition of 17 beta-estradiol-induced beta-galactosidase activity at 10 mu M in the yeast expressing ER alpha, and 42% and 30%, respectively, at 10 mu M in the yeast expressing ER beta. Virtual docking of acetyl mansonone G to ER alpha showed that it binds, with its acetyl oxygen, in a similar way to the 17 beta-OH of estradiol. %26lt;br%26gt;Discussion and conclusion: The phenolic hydroxyl group in mansonones and mansorins was not essential for binding to estrogen receptors. In addition, acetyl mansonone G could represent a promising starting material for the synthesis of anti-estrogenic agents.
- 出版日期2013-8
