Identification of 10-dehydrooxyglycyuralin E as a selective human estrogen receptor alpha partial agonist

[Display omitted] •A scaffold of 2-arylbenzofuran-containing compounds are ligands for ERα.•10-Dehydrooxyglycyuralin E shows partial agonistic activity for ERα in the reporter assay.•10-Dehydrooxyglycyuralin E shows anti-estrogenic/proliferative activity in breast cancer cells.•10-Dehydrooxyglycyura...

Full description

Saved in:

Bibliographic Details
Published in:	Bioorganic chemistry 2019-07, Vol.88, p.102977, Article 102977
Main Authors:	Saito, Nao, Kawase, Keiko, Yamashita, Naoya, Tang, Yingzhan, Wang, Ying, Wang, Jian, Liu, Yongxiang, Li, Ning, Li, Wei, Cheng, Mao-Sheng, Koike, Kazuo, Kanno, Yuichiro, Nemoto, Kiyomitsu
Format:	Article
Language:	eng
Subjects:	Anti-estrogenic activity Anti-proliferative activity Breast cancer Estrogen receptor (ER) Partial agonist Selective estrogen receptor modulators (SERMs)
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	[Display omitted] •A scaffold of 2-arylbenzofuran-containing compounds are ligands for ERα.•10-Dehydrooxyglycyuralin E shows partial agonistic activity for ERα in the reporter assay.•10-Dehydrooxyglycyuralin E shows anti-estrogenic/proliferative activity in breast cancer cells.•10-Dehydrooxyglycyuralin E is a candidate for Selective Estrogen Receptor Modulators (SERMs). Selective estrogen receptor modulators (SERMs) act as either agonist or antagonist of estrogen receptor (ER) in a tissue selective manner and have been used in several diseases such as breast cancer, postmenopausal syndrome, osteoporosis, and cardiovascular diseases. However, current SERMs may also increase the risk of serious side effects and trigger drug resistance. Herein, a screening program, that was designed to search for novel SERMs, resulted in the identification of a series of 2-arylbenzofuran-containing compounds that are ligands for ERα, when applying the Gaussia-luciferase reporter assay. One of these compounds, 10-dehydrooxyglycyuralin E (T9) was chemically synthesized. T9 showed anti-estrogenic/proliferative activity in ERα-positive breast cancer cells. Pretreatment of T9 prevented the mRNA expression of GREB1, which is an estrogen response gene. Furthermore, by an in silico docking simulation study we demonstrated that T9 showed interactions directly to ERα. Taken together, these results demonstrated that T9 is a candidate of SERMs and a useful seed compound for the foundation of the selective activity of SERMs.
ISSN:	0045-2068 1090-2120