title: Structure-activity relationships in non-ligand binding pocket (non-LBP) diarylhydrazide antiandrogens.
abstract: We report the synthesis and a study of the structure-activity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate cancer was evaluated using in vitro time resolved fluorescence resonance energy transfer and fluorescence polarization on target assays. Additionally, a theoretical study combining docking and molecular dynamics methods was performed to provide insight into their mechanism of action as a basis for further lead optimization studies.
authors.affiliation: Molecular Design Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Caboni
authors.forename: Billy
authors.initials: B
authors.lastname: Egan
authors.forename: Brendan
authors.initials: B
authors.lastname: Kelly
authors.forename: Fernando
authors.initials: F
authors.lastname: Blanco
authors.forename: Darren
authors.initials: D
authors.lastname: Fayne
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Meegan
authors.forename: David G
authors.initials: DG
authors.lastname: Lloyd
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006878:Hydroxides / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008024:Ligands; D008745:Methylation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000726:Androgen Antagonists; D006834:Hydrazines; D006878:Hydroxides; D008024:Ligands; D011944:Receptors, Androgen; C029424:hydrazine; C031356:hydroxide ion