Quantitative structure-activity relationship for estrogenic flavonoids from Psoralea corylifolia

文献类型： 外文期刊

第一作者： Zhong, Shuning

作者： Zhong, Shuning;Meng, Yao;Deng, Wenya;Guan, Tianzhu;Zhang, Jie;Li, Tiezhu;Hou, Ligang;Wang, Yongjun;Xing, XiaoJia

作者机构：

关键词： Flavonoids from Psoralea corylifolia; Estrogenic activity; Fluorescence polarization; Computational modeling; QSAR

期刊名称：JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS （ 影响因子：3.935； 五年影响因子：3.563 ）

ISSN： 0731-7085

年卷期： 2018 年 161 卷

页码：

收录情况： SCI

摘要： A combination of in vitro and in silico approaches was employed to investigate the estrogenic activities of flavonoid compounds from Psoralea corylifolia. In order to develop fluorescence polarization (FP) assay for flavonoids, a soluble recombinant protein human estrogen receptor a ligand binding domain (hER alpha-LBD) was produced in Escherichia coli strain. The competition binding experiment was performed by using coumestrol (CS) as a tracer. The result of FP assay suggested that the tested flavonoids can bind to hERa-LBD as affinity ligands, except for corylin. Then, molecular modeling was conducted to explore the binding modes between hER alpha-LBD and flavonoids. All the tested compounds fit into the hydrophobic binding pocket of hER alpha-LBD. The hydrophobic and hydrogen-bonding interactions are dominant forces to stabilize the flavonoids-hER alpha-LBD binding. It can be speculated from molecular docking study that the hydroxyl groups and prenyl group are essential for flavonoid compounds to possess estrogenic activities. Both methylation of hydroxyl group and cyclization of prenyl group significantly diminish the estrogenic potency of flavonoids. Furthermore, quantitative structure-activity relationship (QSAR) analysis was performed by the calculated binding energies of flavonoids coupled with their determined binding affinities. Comparison between the docking scores and the pIC(50) values yields an R-squared value of 0.9722, indicating that the estrogenic potency of flavonoids is structure-dependent. In conclusion, molecular docking can potentially be applied for predicting the receptor-binding properties of undescribed compounds based on their molecular structure. (C) 2018 Elsevier B.V. All rights reserved.

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