Microwave-assisted green synthesis of bile acid derivatives and evaluation of glucocorticoid receptor binding.

Autor: Vasiljević BR; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 3 21 000 Novi Sad Serbia bojana.vasiljevic@dh.uns.ac.rs., Petri ET; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 2 21 000 Novi Sad Serbia., Bekić SS; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 3 21 000 Novi Sad Serbia bojana.vasiljevic@dh.uns.ac.rs., Ćelić AS; Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 2 21 000 Novi Sad Serbia., Grbović LM; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 3 21 000 Novi Sad Serbia bojana.vasiljevic@dh.uns.ac.rs., Pavlović KJ; Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad Trg Dositeja Obradovića 3 21 000 Novi Sad Serbia bojana.vasiljevic@dh.uns.ac.rs.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2020 Nov 19; Vol. 12 (2), pp. 278-287. Date of Electronic Publication: 2020 Nov 19 (Print Publication: 2021).
DOI: 10.1039/d0md00311e
Abstrakt: Herein, we present microwave-assisted AlCl 3 catalyzed oxidation of bile acid hydroxyl groups in the presence of Oxone® in water media. Significant rate enhancements were observed for Wolff-Kishner reduction of synthesized bile acids oxo derivatives to the 5β-cholanic acid. Reaction of amidation of the simplest bile acid and aminolysis of the deoxycholic acid was accomplished in the absence of solvent and catalysts under sealed vessel microwave conditions. Because 5β-cholanic acid reportedly modulates glucocorticoid receptor signaling in cell models of Parkinson's disease, we tested the affinity of 5β-cholanic acid and deoxycholic acid derivatives for the glucocorticoid receptor in vitro using a yeast-based fluorescent screen. Treatment of GR-expressing yeast with prednisolone resulted in a dose-dependent increase in fluorescence; whereas 5β-cholanic acid binds to the glucocorticoid receptor with more moderate affinity. Similarly, molecular docking also suggests that 5β-cholanic acid can bind to the glucocorticoid receptor, with similar geometry to known GR ligands.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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