Quantitative structure-activity relationship for estrogenic flavonoids from Psoralea corylifolia

Autor: Yongjun Wang, Ligang Hou, Tiezhu Li, XiaoJia Xing, Wenya Deng, Shuning Zhong, Tiehua Zhang, Yao Meng, Jie Zhang, Tianzhu Guan
Rok vydání: 2018
Předmět:
0301 basic medicine
Models
Molecular
Quantitative structure–activity relationship
Molecular model
Coumestrol
Stereochemistry
Psoralea corylifolia
In silico
Clinical Biochemistry
Flavonoid
Pharmaceutical Science
Quantitative Structure-Activity Relationship
Fluorescence Polarization
01 natural sciences
Binding
Competitive
Analytical Chemistry
Psoralea
03 medical and health sciences
chemistry.chemical_compound
Prenylation
Drug Discovery
Spectroscopy
chemistry.chemical_classification
Flavonoids
biology
Molecular Structure
Chemistry
fungi
010401 analytical chemistry
Estrogen Receptor alpha
food and beverages
Estrogens
Hydrogen Bonding
biology.organism_classification
0104 chemical sciences
Molecular Docking Simulation
030104 developmental biology
Docking (molecular)
Hydrophobic and Hydrophilic Interactions
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of pharmaceutical and biomedical analysis. 161
ISSN: 1873-264X
Popis: 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 α ligand binding domain (hERα-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 hERα-LBD as affinity ligands, except for corylin. Then, molecular modeling was conducted to explore the binding modes between hERα-LBD and flavonoids. All the tested compounds fit into the hydrophobic binding pocket of hERα-LBD. The hydrophobic and hydrogen-bonding interactions are dominant forces to stabilize the flavonoids-hERα-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 pIC50 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.
Databáze: OpenAIRE
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