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Molecular modeling of the interaction of 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRβ

Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract

Eight isomeric 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides, conformationally rigid oxysterol analogues, differing in the structure of the amide moiety have been analyzed. Analysis of low energy conformers revealed that all 17(20)E-isomers had three main energy minima (corresponding to the values of the dihedral angle θ20,21 (C17=C20-C21=O) about ∼0°, ∼120°, and ∼240°); the most occupied minimum corresponded to θ20,21 about ∼0°. 17(20) Z-Isomers had either one or two pools of stable low energy conformations. Molecular docking of these compounds to the ligand-binding site of the nuclear receptor LXRβ (a potential target) demonstrated high probability of binding of E-isomers but not Z-isomers with this target. 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-3β-hydroxypregna-5,17(20)-dien-21-oyl (hydroxyethyl)amide was demonstrated.

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Correspondence to A. V. Veselovsky.

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Original Russian Text © I.V. Fedyushkina, S.V. Stulov, N.O. Dugin, A.Yu. Misharin, A.R. Mehtiev, G.E. Morozevich, A.V. Veselovsky, 2013, published in Biomeditsinskaya Khimiya.

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Fedyushkina, I.V., Stulov, S.V., Dugin, N.O. et al. Molecular modeling of the interaction of 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRβ. Biochem. Moscow Suppl. Ser. B 7, 196–201 (2013). https://doi.org/10.1134/S1990750813030037

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