Development of docking-based 3D-QSAR models for PPARgamma full agonists
Peroxisome proliferator-activated receptor gamma (PPAR?) has become an attractive molecular target for drugs that aim to treat diabetes mellitus type II, and its therapeutic potency against skin cancer and other skin diseases is also currently being explored. To study the relationship between the structure of several PPAR? full agonists and the trans-activation activity of PPAR?, we have performed a three-dimensional quantitative structureactivity relationship (3D-QSAR) study of tyrosine-based derivatives, based on the 3D alignment of conformations obtained by docking. Highly predictive 3D-QSAR models, with Pearson-R values of 0.86 and 0.90, were obtained for the transactivation activity and binding affinity of PPAR?, respectively. These models are in good agreement with the structural characteristics of the binding pocket of PPAR? and provide some structural insights for the improvement of PPAR? full agonist bioactivities.
lbd ligand binding domain ppar peroxisome proliferator-activated receptor qsar quantitative structureactivity relationship sar structureactivity relationship tzds thiazolidinediones