Molecular Topology Applied to the Discovery of 1-Benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a Non-Ligand-Binding-Pocket Antiandrogen

被引：9
|
作者：
Caboni, Laura [1 ]
Galvez-Llompart, Maria [2 ]
Galvez, Jorge [2 ]
Blanco, Fernando [1 ]
Rubio-Martinez, Jaime [3 ,4 ]
Fayne, Darren [1 ]
Lloyd, David G. [1 ]
机构：
[1] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Mol Design Grp, Dublin 2, Ireland
[2] Univ Valencia, Fac Pharm, Dept Phys Chem, Drug Design & Mol Connect Res Unit, Valencia, Spain
[3] Univ Barcelona, Dept Phys Chem, Barcelona, Spain
[4] Univ Barcelona, Inst Quim Teor & Computac IQTCUB, Barcelona, Spain
来源：
JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2014年 / 54卷 / 10期
关键词：
3; BF3; SITE; ANDROGEN RECEPTOR; ANTIHISTAMINIC COMPOUNDS; ACTIVE-DRUGS; PREDICTION; SEARCH; VALIDATION; CHEMISTRY; TOXICITY; PATTERN;
D O I：
10.1021/ci500324f
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We report the discovery of 1-benzyl-2-(3-fluorophenyl)-4-hydroxy-3-(3-phenylpropanoyl)-2H-pyrrole-5-one as a novel non-ligand binding pocket (non-LBP) antagonist of the androgen receptor (AR) through the application of molecular topology techniques. This compound, validated through time-resolved fluorescence resonance energy transfer and fluorescence polarization biological assays, provides the basis for lead optimization and structureactivity relationship analysis of a new series of non-LBP AR antagonists. Induced-fit docking and molecular dynamics studies have been performed to establish a consistent hypothesis for the interaction of the new active molecule on the AR surface.
引用
收藏
页码：2953 / 2966
页数：14
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