Prenylflavonoids as Nonsteroidal Phytoestrogens and Related Structure-Activity Relationships
ln the search for estrogen receptor (ER) modulators,a series of prenylflavonoids were found to be widely distributed amongst tonic herbal medicines and to possess estrogen-like activity in MCF-7／BOS cells,as evaluated by an estrogen-screening assay．Cell-cycle analysis revealed that the stimulatory effects of these compounds toward cell proliferation were elicited at the G 1-5checkpoint and—Could significantly increase the S-phase population of MCF-7 cells under hormone-free conditions.ER-responsive gene(PSZ PgR)and protein (PgR) expression was also detected；mRNA and protein-expression levels for PS2 and PgR were upregulated by the compounds in a dose-dependent manner．These effects could be inhibited by the pure ER antagonist ICI 182,780((17α-9-4,4,5,5,5-pentafluoropentylsulfinylnonyl)estra-1,3,5(10)．triene-3,17β-diol)．It was therefore concluded that the estrogen-like effects of these prenylflavonoids were mediated primany through ERs．Furthermore,to explore the structure-activity relationship based on the estrogen receptor and detailed molecular mechanisms among the prenylflavonoids,protein-ligand docking simulations were carried out by using the DS-MODELING software package．The bingding affinity of each prenylflavonoid toward ERα was scored,and the receptar-ligand interaction was also anaiyzed to provide the simulation characteristics of virtual molecular recognition mechanisms．
Zhi-qiang Wang Nadine Weber Yi-jia Lou Peter Proksch
Department of Pharmacology and Toxicology College of Pharmaceutical Sciences Zhejiang University, Ha Institut für Pharmazeutische Biologic Heinrich-Heine-Universitat Düsseldorf Universitatsstraβe 1, Ge
国际会议
杭州
英文
1224-1230
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）