Molecular Docking Studies of Glycyrrhizic acid (GA), Glycyrrhetic acid (GE) and Glabridin (GLA) With Estrogen Receptors (Ers)

J. Ling, D. L. Oh and A. Y. Y. Chia

School of Biosciences, Taylor’s University, Lakeside Campus, Jalan Taylor’s, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia.

Corresponding Author E-mail: sukdv84@gmail.com

DOI : http://dx.doi.org/10.13005/bbra/2411

ABSTRACT: Treating post-menopausal symptoms with hormone replacement therapy is associated with various health risks. Alternatively, licorice root is often used to relief post-menopausal symptoms in traditional medicine. The bioactive components of licorice root, such as GA, GE and GLA, have been previously studied in vitro for their estrogenic effects. In this study, they were subjected to molecular docking study to further acknowledge their estrogenicity. GA and GE showed positive binding energy in the molecular docking study, suggesting that they could not bind nor activate ERs. Intermolecular interaction analysis identified multiple sites of unfavorable steric bumps, indicating pentacyclic structure and methyl side groups of GA and GE were detrimental to formation of energy favorable positions in ligand binding cavity of ERs. On the other hand, GLA could be docked into the ligand binding cavity of ERs, though with comparatively higher binding energy to that of 17β-estradiol (E₂). It was observed that the rotatable 1,3-benzenediol of GLA is essential for GLA-ERs binding. Furthermore, oxidation of the methyl side groups of GLA might improve the binding affinity. In conclusion, GLA, not GA and GE, is a partial ERs agonist and could be further modified to design novel semi-synthetic post-menopausal drugs.

KEYWORDS: Estrogen receptor (ER); GLA, Glabridin acid (GLA); Glabridin acid (GLA)Molecular docking;

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