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) Е -pregna-5,17(20)-dien-21-oyl amides differing in structure of the amide moiety. Analysis of the low energy сonformers revealed that all 17(20) E -isomers had three main energy minima (corresponding to values of the dihedral angle q (С17=C20-C21=O) ~ 0°, ~ 120° and ~ 240°), the most occupied minimum was found to correspond to q ~ 0°; 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 LXRb (a potential target) indicates high probability of binding for Е -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) Е -3b-hydroxypregna-5,17(20)-dien-21-оyl (hydroxyethyl)amide was demonstrated.
Fedyushkina I.V., Stulov S.V., Dugin N.O., Misharin A.Yu., Mehtiev A.R., Morozevich G.E., Veselovsky A.V. (2013) Molecular modeling of interaction of 17(20) and 17(20) E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRb. Biomeditsinskaya Khimiya, 59(3), 321-329.
Fedyushkina I.V. et al. Molecular modeling of interaction of 17(20) and 17(20) E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRb // Biomeditsinskaya Khimiya. - 2013. - V. 59. -N 3. - P. 321-329.
Fedyushkina I.V. et al., "Molecular modeling of interaction of 17(20) and 17(20) E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRb." Biomeditsinskaya Khimiya 59.3 (2013): 321-329.
Fedyushkina, I. V., Stulov, S. V., Dugin, N. O., Misharin, A. Yu., Mehtiev, A. R., Morozevich, G. E., Veselovsky, A. V. (2013). Molecular modeling of interaction of 17(20) and 17(20) E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRb. Biomeditsinskaya Khimiya, 59(3), 321-329.
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