QSAR studies for some thiazolidine-2,4-dione derivatives as PIM-2 kinase inhibitors |
| |
Authors: | Vivek Asati Sanjay K. Bharti |
| |
Affiliation: | 1.Institute of Pharmaceutical Sciences,Guru Ghasidas Vishwavidyalaya (A Central University),Bilaspur,India |
| |
Abstract: | Quantitative structure–activity relationship (QSAR) studies were performed on a series of 21 thiazolidine-2,4-dione derivatives to find the structural requirements for PIM-2 kinase inhibitory activity by two-dimensional (2D-QSAR), group-based (G-QSAR) and three-dimensional (3D-QSAR) studies. In the present study, widely used technique viz. stepwise forward–backward (SW-FB) has been applied for the development of 2D- and G-QSAR as variable selection method. The statistically significant best 2D-QSAR model was developed by partial least squares regression (PLSR) having r 2 = 0.78, q 2 = 0.63 with pred_r 2 = 0.78. The statistically significant best G-QSAR model was developed by PLSR method having r 2 = 0.89, q 2 = 0.79 and pred_r 2 = 0.82. The 3D-QSAR studies were performed by k-nearest neighbor molecular field analysis along with genetic algorithm method which showed q 2 = 0.64 and pred_r 2 = 0.94. A docking study revealed the binding orientations of these inhibitors at active site amino acid residues (PHE 43, ASP 124, ASP 182 and GLU 83) of PIM-2 enzyme (PDB ID: 3IWI). The results of this study may be useful to (medicinal) chemists to design more potent thiazolidine-2,4-dione analogs as PIM-2 kinase inhibitors. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|