title: [Molecular modeling of interaction of 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRbeta].
abstract: Aiming the search of novel regulators of lipid metabolism and their potential targets, in this study we performed molecular modeling of eight isomeric 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides differing in structure of the amide moiety. Analysis of the low energy conformers revealed that all 17(20)E-isomers had three main energy minima (corresponding to values of the dihedral angle theta20,21 (C17 = C20-C21 = 0) to approximately 0 degrees, to approximately 120 degrees and to approximately 240 degrees), the most occupied minimum was found to correspond to theta20,21 to approximately 0 degrees; while 17(20)Z-isomers had either one or two pools of low energy conformations. Molecular docking of these compounds to the ligand-binding site of the nuclear receptor LXRbeta (a potential target) indicates high probability of binding for E-isomers and the absence of that for Z-isomers. Results of the molecular modeling were confirmed by an experiment in which stimulation of triglyceride biosynthesis in Hep G2 cells in the presence of 17(20)E-3beta-hydroxypregna-5,17(20)-dien-21-oyl (hydroxyethyl)amide was demonstrated.
authors.forename: I V
authors.initials: IV
authors.lastname: Fediushkina
authors.forename: S V
authors.initials: SV
authors.lastname: Stulov
authors.forename: N O
authors.initials: NO
authors.lastname: Dugin
authors.forename: A Iu
authors.initials: AIu
authors.lastname: Misharin
authors.forename: A R
authors.initials: AR
authors.lastname: Mekhtiev
authors.forename: G E
authors.initials: GE
authors.lastname: Morozevich
authors.forename: A V
authors.initials: AV
authors.lastname: Veselovskiĭ
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D000071518:Liver X Receptors; D062105:Molecular Docking Simulation; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D014280:Triglycerides / Q000096:biosynthesis*
chemical_list: D000577:Amides; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D014280:Triglycerides