Quantitative Structure Activity Relationship Studies of A Novel Class of Dual PPAR γ/δ Agonists

The Peroxisome proliferators-activated receptors (PPARs) constitute a highly conserved set of ligand activated transcription factors in the nuclear hormone receptor subfamily. Selective modulation of PPAR could provide significant anti-diabetic activity with the reduction or elimination of side effects. These have increasingly become attractive targets for developing novel anti-type 2 diabetic drugs. In the present study the QSAR analysis was performed employing V-life MDS-3.0 software to retrieve information about structure activity relationships of some 3-{4-[3-(2aryl-phenoxy)butoxy]-phenyl}propionic acids as novel PPAR γ/δ agonists. 2D QSAR methods were developed using Partial Least Square (PLS) and variable selection methods. Out of the 10 models developed, the two best 2D QSAR models having highest correlation coefficient and cross validated squared correlation coefficient were selected for further study, which are r = 0.9581, q = 0.9262, F test = 160.2108, pred_r = 0.3840, pred_rse = 0.6413 and r = 0.9440, q = 0.8987, F test = 118.1064, pred_r = 0.5371, pred_rse = 0.5559. 3D QSAR models were developed using kNN-MFA method, combined with simulated annealing selection procedure. Out of the 10 models developed the best 3D QSAR model having highest cross validated squared correlation coefficient was selected for further study, record as q = 0.8184, Pred_r = 0.7455.