Prenylflavonoids as Nonsteroidal Phytoestrogens and Related Structure-Activity Relationships

摘要

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-pentafluoropentyl}sulfinyl]nonyl)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．