Involvement of a Hydrophobic Pocket and Helix 11 in Determining the Modes of Action of Prenylated Flavonoids and Isoflavonoids in the Human Estrogen Receptor

M.G.M. van de Schans, T. Ritschel, T.F.H. Bovee, M.G. Sanders, P. de Waard, H. Gruppen, J.P. Vincken

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

Abstract

Six prenylated (iso)flavonoids were purified from a licorice root extract and subjected to competition experiments with six commercially available (iso)flavonoids. The agonistic and antagonistic activities of these compounds towards both hERa (human estrogen receptor alpha) and hERb were determined. Differences in the modes of action (agonist or antagonist) were observed for the various compounds tested. In general, each compound had the same mode of action towards both ERs. In silico modeling was performed in order to study the differences in estrogenicity observed between the compounds. It is suggested that prenyl chains fit into a hydrophobic pocket present in the hER, resulting in an increased agonistic activity. In addition, it was shown that an increase in length (…1.7 æ) of pyran prenylated isoflavonoids resulted in an antagonistic mode of action. This might be caused by collision of the pyran ring with helix 11 in the ligand binding cavity of the hER.
Original languageEnglish
Pages (from-to)2668-2677
JournalChemBioChem
Volume16
Issue number18
DOIs
Publication statusPublished - 2015

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