Title:Molecular Docking, 3D-QSAR and Structural Optimization of Indole Biphenylcarboxylic Acids as PPARγ Antagonists
Volume: 14
Issue: 8
Author(s): Xin Liu, Yu-Ze Zhang, Zhi Jing, Wen-Qing Jia, Shu-Qing Wang, Wei-Ren Xu and Xian-Chao Cheng*
Affiliation:
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070,China
Keywords:
3D-QSAR, antidiabetic, indole biphenylcarboxylic acids, molecular docking, PPARγ , structural optimization.
Abstract: 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 r
2 is 0.995, test set r
2 is 0.614, the model also has
a cross-validation q
2 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.
