Molecular Docking and SAR Studies of Thiazolidinone Compounds Against Cox-2

Abstract

This article reviews the possibility of new thiazolidinone derivatives as Cyclooxygenase-2 (COX-2) selective inhibitors in terms of the molecular docking and Structure-Activity Relationship (SAR) analysis. Ten derivatives (TZD-1 to TZD-10) were selected, designed, modeled, and docked in COX-2 active site (PDB ID: 5IKR) with the help of AutoDock Vina and PyRx. The binding affinities, forms of interactions, as well as amino acids involved were documented in order to evaluate inhibitory potentials. Compounds with the best activity (TZD-4, TZD-2 and TZD-10) had a large interaction with catalytically essential residues (Ser530, Tyr355 and Arg120) with the score of binding 10 kcal/mole or less. SAR analysis demonstrated the insufficient negative linear correlation between the lipophilicity (logP) and the binding score (r = -0.62, p = 0.047), which implies that moderately lipophilic derivates bind the COX- Molecular weight on the other hand was weakly significantly correlated with binding affinity. The results give insight of the structural and physicochemical properties that play a part in COX-2 inhibition and rational construction of thiazolidinone-bearing anti-inflammatory agents.