Molecular Docking, 3D-QSAR and Structural Optimization of Indole Biphenylcarboxylic Acids as PPARγ Antagonists

Background: Recent studies indicated that indole biphenylcarboxylic acids exhibited antidiabetic properties in diet-induced obese mice through antagonism of PPAR.γ Objective and Method: In order to explore structure activity relationship and the interactions with PPARγ, thus finding new active compounds, we carried on some researches by molecular docking and 3D-QSAR studies. We also explored structure activity relationship of these compounds by 3DQSAR studies. A Partial Least Squares (PLS) model was built using energy grids as descriptors. Results and Conclusion: This model of training set r2 is 0.995, test set r2 is 0.614, the model also has a cross-validation q2 value of 0.556. According to the molecular docking results and contour maps derived from the 3D-QSAR model, we carried out structural optimization and designed several new compounds to improve the predicted biological activity and dock scores of original ones. The new compounds could offer a possible orientation for finding potential drugs.