Pharmacophore-based Virtual Screening and In-vitro activity Evaluation of alpha Chymotrypsin Inhibitors.

Virtual screening is a high through put technique which provides useful information towards drug designing and discovery process in a timely manner. In our case of study, we used in silico prediction methods (structure-based and ligand-based) to identify drug-like candidates using our in-house data-base against ?-chymotrypsin enzyme. Over expression of ?-chymotrypsin is associated with various gastro intestinal tract (GIT) disorders such as intestinal bowel syndrome (IBS), gastro esophageal reflux disease (GERD) and Crohn\\\'s disease. Chymostatin is the most commonly available drug used for the treatment, but due to its hepatic toxicity and protein degradation of skeletal muscles, there is a strong need to develop new ?-chymotrypsin inhibitors with improved potency and reduce toxic effects. From our current study we identified nineteen hits which were further subjected for in-vitro screening. Experimentally eight compounds showed inhibition against ?-chymotrypsin receptor; while three compounds considered as good inhibitors with an IC50 value of 319.8, 474.8 and 481.3 ?M, respectively.