In-Silico Analysis of various Benzilate Derivatives towards Cyclooxygenase 2 Enzyme

Cyclooxygenases (COX-1 and COX-2) catalyze the rate-limiting step in the biosynthesis of prostaglandins, prostacyclins, and thromboxanes. Ibuprofen has classically fallen into the time-dependant class of COX inhibitors as it binds rapidly and reversibly to Cox and acts as a competitive inhibitor of arachidonic acid oxygenation.The discovery of new and novel anti-inflammatory drugs is an area of intense interest in both pharmaceutical industry and academic laboratories. Significant advances have been made in the treatment of inflammatory diseases such as rheumatoid arthritis and multiple sclerosis, but most dramatically with new biologic agents. Perhaps due in part to the mixed experiences with COX-2 inhibitors, very few small molecule anti-inflammatory drugs with novel modes of action have made it to the market in the last decade.The various benzilic acid compounds synthesized have taken for in-silico analysis to study the structure activity relationship using crystal structure co-crystallized with 2-(4-isobtyl phenyl) propionic acid (PDB ID: 4PH9).The synthesized ligands were docked using three different docking strategies; High throughput virtual screening, Standard Precision and Extra Precision docking strategies. After three different analyses, the docking scores of the synthesized compounds were found to be in the range of -8.221 to –6.342 Kcal mol-1. Finally the compounds are shortlisted based on the visual inspection of the amino acids interaction.