Screening the binding affinity of bile acid derivatives for the glucocorticoid receptor ligand-binding domain Scientific paper

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Srđan Bjedov
Sofija Bekić
Maja Marinović
Dušan Škorić
Ksenija Pavlović
Anđelka Ćelić
Edward Petri
Marija Sakač


The necessity of anti-inflammatory drugs such as glucocorticoids has been evident during the COVID-19 pandemic. Glucocorticoids, are the stan­dard therapy for the treatment of moderate and severe COVID-19 patients. However, serious side effects limit the use of these drugs, and anti-inflam­matory drugs with better pharmacological properties are urgently required. Bile acids are of interest, because of their anti-inflammatory and immunomodul­atory properties, facilitated through an unclear mechanism involving trans­mem­brane and nuclear receptors. In this work, we screened the binding activity of a number of bile acid deri­vatives, for the ligand-binding domain of glucocor­ticoid receptor (GR-LBD), the most important receptor for anti-inflammatory processes. Tested compounds inc­lude oximes, lactones, lactams, tetrazoles, dienones, C-24 alcohols and cholic acid amides. Cholic acid oxime, deoxy­cho­lic acid dienone, 3-keto-24-cholic alcohol and cholic acid amide showed best binding affinities for GR-LBD among tested compounds. The in silico mole­cular docking explanation is provided. SAR analysis showed that expansion of B and C steroid rings or attachment of hetero­cycle to C ring is not beneficial for binding; side chain should contain hydrogen donor group; the GR-LBD tolerate well different functionalities on C-3 position. These results provide valu­able information toward synthesis of the new gluco­corticoids based on bile acids.


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How to Cite
S. Bjedov, “Screening the binding affinity of bile acid derivatives for the glucocorticoid receptor ligand-binding domain: Scientific paper”, J. Serb. Chem. Soc., vol. 88, no. 2, pp. 123–139, Dec. 2022.
Organic Chemistry
Author Biography

Maja Marinović, Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000, Novi Sad, Serbia


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