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

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Srđan Bjedov
https://orcid.org/0000-0002-9630-5831
Sofija Bekić
https://orcid.org/0000-0002-9020-698X
Maja Marinović
https://orcid.org/0000-0001-8696-7148
Dušan Škorić
https://orcid.org/0000-0002-3683-0255
Ksenija Pavlović
https://orcid.org/0000-0001-6339-1350
Anđelka Ćelić
https://orcid.org/0000-0002-1058-6872
Edward Petri
https://orcid.org/0000-0002-3650-1523
Marija Sakač
https://orcid.org/0000-0002-2796-1296

Abstract

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
[1]
S. Bjedov, “Screening the binding affinity of bile acid derivatives for the glucocorticoid receptor ligand-binding domain: Scientific paper”, J. Serb. Chem. Soc., Sep. 2022.
Section
Organic Chemistry

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