Molecular modeling studies of some thiazolidine-2,4-dione derivatives as 15-PGDH inhibitors

The quantitative structure–activity relationship (QSAR) studies were performed on a series of 34 thiazolidine-2,4-dione derivatives to find the structural features necessary for the inhibition of 15-PGDH. The multiple linear regression (MLR) and partial least square (PLS) regression coupled with stepwise (SW) feature selection methods were performed to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The statistically significant 2D-QSAR model having r2 = 0.71, 0.71 and q2 = 0.62, 0.62 with pred_r2 = 0.93, 0.88 was developed by SW-PLS and SW-MLR consecutively. Molecular field analysis was used to construct the best 3D-QSAR model using k-nearest neighbor (kNN) method, which showed good correlative and predictive capabilities in terms of q2 = 0.78 and pred_r2 = 0.74. A docking study revealed the binding orientations of these inhibitors at active site amino acid residues (ASN-91, GLY-93, GLY-12, TRY-151) of 15-PGDH enzyme (PDB ID: 2GDZ).