IN SILICO STUDIES OF PREDNISOLONE ACETATE DERIVATIVES FOR THE TREATMENT OF DRY EYE DISEASE

Abstract

An attempt was made to find a potential cure for the dry eye syndrome affecting millions of people around the globe eventually leading to inflammation, blurry vision, irritation, redness, and ocular pains. In this condition, the tears are unable to provide enough lubrication either due to the lack of adequate tears or generation of poor-quality tears. The pressing need to find a cure to this chronic disease led to the search for a potential anti-inflammatory drug with the help of molecular studies. Molecular docking studies were used to find the potential anti-inflammatory drug. The study used the glucocorticoid receptor in the eye (PDB Id: 6DXK) as our target protein and A HJ4 801 as our ligand for the binding studies. The CRESSET Flare software was used for the in-silico studies of 152 derivatives and the target glucocorticoid protein receptor. Further, ADMET screening was performed to evaluate parameters like lipophilicity, polarity, solubility, Lipinski rule, and bioavailability score. Swiss ADME, web-based software was used to perform these studies, and further strengthen our result. Out of 152 compounds that were studied for molecular docking, 18 compounds namely Deprodone propionate, Methylprednisolone aceponate, Prednisolone valerate acetate, Methylprednisolone hemisuccinate, and pred forte, etc. were found to possess a better score than prednisolone acetate. All the molecules were found to have molecular size (less than 500 Da), aqueous solubility (soluble, moderately soluble), lipophilicity scores (less than 5) that serve as a good candidate for ocular permeability. The toxicity studies also showed no ocular irritation or corrosion. The high binding affinity of the target glucocorticoid protein receptor with the ligands can be seen as a potential treatment for dry eye disease. It serves as the basis for introducing better compounds that act as an efficient antiinflammatory agent by inhibiting the glucocorticoid receptor and having a high binding affinity. The ADME studies showed significant bioavailability and permeability across the cornea. The top five molecules pursued properties necessary to be a good candidate for ocular absorption. Screening more compounds from various databases and performing clinical trials can be an effective strategy to further validate the results eventually leading to the discovery of less toxic and efficacious compounds for curing dry eye syndrome.