文献类型：期刊文献

英文题名：Discovery of natural estrogen receptor modulators with structure-based virtual screening

作者：Cao, Xianwen[1];Jiang, Jing[1];Zhang, Shoude[1,2];Zhu, Lili[1];Zou, Juan[3];Diao, Yanyan[1];Xiao, Weilie[3];Shan, Lei[4];Sun, Handong[3];Zhang, Weidong[2,4];Huang, Jin[1];Li, Honglin[1]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China;[3]Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West, Kunming 650201, Yunnan, Peoples R China;[4]Second Mil Med Univ, Sch Pharm, Dept Phytochem, Shanghai 200433, Peoples R China

年份：2013

卷号：23

期号：11

起止页码：3329

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000318976100040)】；

基金：This work was supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China, the Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants 21173076, 81102420, 81102375, 81230090 and 81222046), the Special Fund for Major State Basic Research Project (Grant 2009CB918501), the Shanghai Committee of Science and Technology (Grants 11DZ2260600 and 12401900801), the 863 Hi-Tech Program of China (Grant 2012AA020308), and the National S&T Major Project of China (Grant 2011ZX09307-002-03). Honglin Li is also sponsored by Program for New Century Excellent Talents in University (Grant NCET10-0378).

语种：英文

外文关键词：Molecular docking; Natural product; Estrogen receptor; Virtual screening

摘要：Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ER alpha and ER beta. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 mu M for ERa and ERb, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation. (C) 2013 Elsevier Ltd. All rights reserved.