title: The systematic structure-activity relationship to predict how flavones bind to human androgen receptor for their antagonistic activity.
abstract: Although flavones act as potent androgen receptor (AR) antagonists, it remains unclear how flavones interact with AR. The aim of this in silico study was to investigate the molecular recognition processes of newly synthesized 5,4'-difluoroflavone with the highest activity (IC50 value=0.19 μM) in the AR-ligand binding domain (AR-LBD). The results demonstrated that at its 4'-position of 5,4'-difluoroflavone the substituents may face Arg752 and that in AR-LBD, the submolecular bulk of substituents is unfavorable for AR antagonists and the negative electrostatic interaction site prefers the stronger hydrogen bond capability of substituents of AR antagonists. The prediction model is a valuable tool for designing a novel AR antagonist.
authors.affiliation: Department of Environmental Bioscience, Meijo University, Nagoya 468-8502, Japan. hiroto@meijo-u.ac.jp
authors.forename: Hiroto
authors.initials: H
authors.lastname: Tamura
authors.forename: Maiko
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Momoko
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Akifumi
authors.initials: A
authors.lastname: Hosoda
authors.forename: Masato
authors.initials: M
authors.lastname: Matsugi
authors.forename: Miki
authors.initials: M
authors.lastname: Akamatsu
mesh_terms: D059002:Androgen Receptor Antagonists / Q000737:chemistry*; D001665:Binding Sites; D015195:Drug Design; D047309:Flavones / Q000737:chemistry*; D054879:Halogenation; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011944:Receptors, Androgen / Q000737:chemistry*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: C410798:AR protein, human; D059002:Androgen Receptor Antagonists; D047309:Flavones; D011944:Receptors, Androgen