Evaluation of Biological Activity and Computer ‐Aided Design of New Soft Glucocorticoids

In this study, local anti‐inflammatory activity of these derivatives was evaluated by use of the croton oil‐induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D‐QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand‐based and structure‐based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24‐1, 25‐1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity. Local anti‐inflammatory activity and systemic side effects were evaluated for a group of novel 17β‐carboxamide steroids, indicating that these compounds are potentially new soft glucocorticoids. Using 3D‐QSAR analysis of these results and virtual screening of the ChEMBL library, novel derivatives were designed and eight compounds with the highest predicted local anti‐inflammatory activity and relative glucocorticoid receptor binding affinity (20, 22, 24‐1, 25‐1, 27, VS7, VS13, and VS14) were selected.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research