Citation: Hui FENG, Xi-Hua DU, Yan CHEN, Chang-Jun FENG. 3D-QSAR Models of Anti-tumor Activity for Histone Deacetylase Inhibitors Containing Dihydropyridin-2-one[J]. Chinese Journal of Structural Chemistry, ;2020, 39(5): 855-860. doi: 10.14102/j.cnki.0254–5861.2011–2534 shu

3D-QSAR Models of Anti-tumor Activity for Histone Deacetylase Inhibitors Containing Dihydropyridin-2-one

School of Chemistry & Chemical Engineering, Xuzhou University of Technology, Xuzhou, Jiangsu 221018, China

Corresponding author: Chang-Jun FENG, fengcj@xzit.edu.cn
Received Date: 16 July 2019
Accepted Date: 25 September 2019

Fund Project: the National Natural Science Foundation of China 21075138special fund of State Key Laboratory of Structure Chemistry 20160028

Figures(3)

A 3D-QSAR study was conducted to analyze the anti-tumor activity (pHs, s = 1, 6) of dihydropyridin-2-one containing histone deacetylase inhibitor (DHDACi) to histone deacetylase (HDACs, s = 1, 6) by the comparative molecular field analysis (CoMFA) method. The predicting model was established based on the training set of 22 compounds, which was verified by the test set of 6 compounds containing template molecule. The results showed that the contributions of steric and electrostatic fields to pH₁ are 37.6% and 62.4%, and those to pH₆ are 44.6% and 55.4%, respectively. The coefficients of the cross-validation (R_cv²) and the non cross-validation (R²) are 0.574 and 0.947 for pH₁, and 0.488 and 0.884 for pH₆, respectively. The models were then used to predict the activities of the compounds for the training and testing sets. The results indicated that the models had strong stability and good predictability. Based on the 3D contour maps, several new potential inhibitors with higher anti-tumor activity were designed. However, the effectiveness of these potential inhibitors is still needed to be verified by the experimental results.
- dihydropyridin-2-one,
- histone deacetylase inhibitor,
- anti-tumor activity,
- 3D-QSAR,
- comparative molecular field analysis
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