PHARMACOPHORE ELUCIDATION AND DOCKING STUDIES ON ANTI-INFLAMMATORY COMPOUNDS OF MEDICINAL PLANTS FOR ULCERATIVE COLITIS
Inflammatory bowel diseases such as Ulcerative Colitis (UC) are becoming common in this aging society throughout the world which includes formation of ulcers or open sores. Since, there is no known medical cure for UC; the therapeutic armamentarium is aimed at reducing the signs and symptoms associated with the disorder. The role of antibiotics in the treatment of severe active UC is controversialbecause the clinically used anti-inflammatory drugs suffer from the disadvantage of side effects and high cost of treatment. In the present study, NF-kB p50/p65 is docked in two different ways, one with the glucocorticoid receptor protein using ZDOCK in Accelrys Discovery Studio 3.5 and the other is screening and docking of400 anti-inflammatory natural compounds derived from plant source which offer a great hope in the identification of lead compounds.These compounds were investigated for their inhibitory activity by molecular docking studies and ADME/T properties of the compounds were analyzed for drug like candidates by using the commercial software's Accelrys Discovery Studio, Lead-IT and GOLD 5.1. Based on the docking results and toxicity analysis using TOPKAT, the best compounds determined are Ginkgetin, Bilobetin and Mesuaxanthone_B. The Pharmacophore studies have also shown that these compounds are having very less side effects and further investigations are requiredto take into clinical trials.
KEYWORDS: Inflammatory bowel disease, NF-kB p50/p65, Glucocorticoid, ZDOCK, TOPKAT
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