Study of Anti-inflammatory Activity of New Derivative of Indomethacin: A Computational Study

Abstract

This article presents the synthesis of new derivative from thiodaizole, based on the reaction of Thiosemicarbazide with Indomethacin in the presence of Phosphorus (V) oxychloride as catalyst. COX enzyme is divided to two isoforms COX-1 and COX-2 with similar structure and high sequence identity. The novel Inhibitor used a thiodaizole ring in combination with Indomethacin to reduce the risk of analogs interfering with COX-1’s small hydrophobic tunnel. Furthermore, the absence of a carboxylic group in the new Inhibitor reduces the Inhibitor’s ability to form a salt bridge with Arg120 (Figure 2), preventing the inhibition of the COX-1 enzyme. The aim of this study is to investigate the Anti-inflammatory activity of Indomethacin against the human second isoform of prostaglandin synthase (cyclooxygenase, COX-2). COX-2 enzyme 3D structures (PDB ID: 1CVU) were extracted from the protein databank. The PDB format of Indomethacin and its derivative were prepared by use Discovery Studio 2016 Client. Molecular docking study appeared that the new derivative exhibited better binding energy (-10.9 kcal/mol) compared with Indomethacin that have binding energy (-10.09 kcal/mol) and it’s have high selectivity towered COX-2 enzyme in the other hand In the present study, the predicted Pharmacokinetic (PK) values of Inhibitor (1) and Indomethacin (NSAID) deduce that Inhibitor (1) satisfies all PK parameters and has qualified as best lead candidate as an Anti-inflammatory agent compared to Indomethacin