A molecular docking study of estrogenically active compounds with 1,2-diarylethane and 1,2-diarylethene pharmacophores.

TitleA molecular docking study of estrogenically active compounds with 1,2-diarylethane and 1,2-diarylethene pharmacophores.
Publication TypeJournal Article
Year of Publication2004
JournalBioorganic & medicinal chemistry
Volume12
Issue24
Pagination6527-37
Date Published2004
ISSN0968-0896
Abstract

Numerous selective estrogen receptor modulators (SERMs) have been synthesized and assayed in recent years. The focus of this study is to apply coarse-grain molecular docking procedures coupled with fine-grain all-atom force field optimization strategies to shed light on the binding mechanisms of currently available estrogen receptor-active compounds. Although the mechanics of ligand binding in estrogen receptors is generally well understood, there is room for surprises. In this paper computational evidence corroborating the experimentally observed type I agonistic binding mode for estradiol (E2) and diethylstilbesterol (DES) and the type II antagonistic binding mode for 4-hydroxytamoxifen and raloxifen is presented. Included in this type I agonistic mode are the DES derivatives, transstilbene and 1,2-diaryldiaminoethane. In addition, a novel 'type II agonistic' binding mode for 2,3-diarylimidazolines, 4,5-diarylimidazoles, 2,3-diarylpiperazines is introduced. This mode is stabilized by suggesting alternative hydrogen bond anchor points in the ligand binding domain as potential leads for future drug design.

URLhttps://linkinghub.elsevier.com/retrieve/pii/S0968-0896(04)00718-7
DOI10.1016/j.bmc.2004.09.022
Short TitleBioorg Med Chem
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