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

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 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.

Cite this article as:

Liu Xin, Zhang Yu-Ze, Jing Zhi, Jia Wen-Qing, Wang Shu-Qing, Xu Wei-Ren and Cheng Xian-Chao*, Molecular Docking, 3D-QSAR and Structural Optimization of Indole Biphenylcarboxylic Acids as PPARγ Antagonists, Letters in Drug Design & Discovery 2017; 14 (8) . https://dx.doi.org/10.2174/1570180814666161207130047

DOI https://dx.doi.org/10.2174/1570180814666161207130047	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X