Abstract

2D- AND 3D-QSAR STUDIES ON THIAZOLIDINE-2,4-DIONE DERIVATIVES

Manoj Upadhyay, Md. Asif, Kohit Sahu, Vivek Asati, Jagdish Chandra Rathi*

ABSTRACT

A series of 21 thiazolidine-2,4-dione derivatives were used for quantitative structure–activity relationship (QSAR) studies. These compounds were introduced into two-dimensional (2D-QSAR), and three-dimensional (3D-QSAR) studies to find the structural requirements for PIM-2 kinase inhibitory activity. The stepwise forward-backward (SW-FB) variable selection method has been applied for the generation of 2D-QSAR. The best 2D-QSAR model generated by partial least squares regression method having r2 = 0.78; q2 = 0.63 with pred_r2 = 0.78. The k-nearest neighbor (kNN) with genetic algorithm(GA) method has been applied for the generation of The 3D-QSAR models having q2 = 0.64 and pred_ r2 = 0.94 values. The docking study showed the binding orientations of these inhibitors at active site amino acid residues (ASP 124, ASP 182, PHE 43 and GLU 83) of PIM-2 enzyme (PDB ID: 3IWI). The results showed the important sites of thiazolidine-2,4-dione analoges for the generation of potent compounds against PIM-2 kinase.

Keywords: G-QSAR, kNN-MFA, Thiazolidine-2,4-dione, 2D/3D QSAR.