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

Author(s): Xin Liu, Yu-Ze Zhang, Zhi Jing, Wen-Qing Jia, Shu-Qing Wang, Wei-Ren Xu, Xian-Chao Cheng*.

Journal Name: Letters in Drug Design & Discovery

Volume 14 , Issue 8 , 2017

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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.

Keywords: 3D-QSAR, antidiabetic, indole biphenylcarboxylic acids, molecular docking, PPARγ , structural optimization.

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Article Details

VOLUME: 14
ISSUE: 8
Year: 2017
Page: [959 - 973]
Pages: 15
DOI: 10.2174/1570180814666161207130047
Price: $58

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