Designing, Cytotoxic Evaluation, Molecular Docking and in Silico Pharmacokinetic Prediction of New Hydrocortisone Derivatives as Anti-Asthmatics Drugs
A series of new 20 corticosteroids were subjected to molecular property prediction. The Molecular, Physicochemical, and Biological properties were determined using Molinspiration Cheminformatics software. These compounds were further subjected to Toxicity Predictions using the Osiris Software. The calculated drug-related properties of the designed molecules were similar to those found in most marketed drugs. Amongst the proposed molecules, fourteen promising candidates can be considered as promising structures for the synthesis of new and more effective anti-asthmatic drugs. Result indicates that the derivatives are orally active molecules. In-silico ADME and toxicity prediction was accomplished with the help of Swiss-ADMET tool provides the latest and most inclusive for diverse chemicals associated with known Absorption, Distribution, Metabolism, Excretion and Toxicity profiles. furthermore, BBB (Blood brain barrier) penetration, HIA (Human intestinal absorption), Caco-2 cell permeability and Ames test were calculated using ADMET web-based query tools incorporating a molecular build in interface enable the database to be queried by Smiles and structural similarity search. According to molecular docking results, derivatives No 4, 10 and 11 showed better docking Scores values compared to other derivatives and also dexamethasone and hydrocortisone.
Keywords: Corticosteroids, Drug-likeness, Lipophilicity, Anti-asthmatic, ADME.
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