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

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