Citation: Zhen ZHANG, Ping CHENG, Yuan-Zheng ZHU, Qiang XIA, Shu-Ping ZHANG. 3D-QSAR Analysis of a Series of 1, 2, 3-Triazole-chromenone Derivatives as an Acetylcholinesterase Inhibitor against Alzheimer's Disease[J]. Chinese Journal of Structural Chemistry, ;2020, 39(7): 1235-1242. doi: 10.14102/j.cnki.0254–5861.2011–2570 shu

3D-QSAR Analysis of a Series of 1, 2, 3-Triazole-chromenone Derivatives as an Acetylcholinesterase Inhibitor against Alzheimer's Disease

College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China

Corresponding author: Shu-Ping ZHANG, zhang_lucy9999@vip.126.com
Received Date: 16 August 2019
Accepted Date: 18 November 2019

Figures(6)

Chromenones have attracted much attention since they are excellent acetylcholinesterase inhibitor (AChEi). The 1, 2, 3-triazoles are multifunctional anti-acetylcholinesterase (AChE) agents. In this paper, we report the three-dimensional quantitative structure-activity relationship (3D-QSAR) study of 25 1, 2, 3-triazole-chromenone derivatives based comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). To construct CoMFA and CoMSIA models, the 25 active molecules were randomly divided into the training and test sets. The obtained cross-validation Q² of the CoMFA model, the coefficient of non-cross-validation R², and the test value F are 0.597, 0.994, and 396.726, respectively. The cross-validation Q² of the CoMSIA model, the coefficient of the non-cross-validation R², and the test value F are 0.721, 0.979, and 131.107, respectively. The predictive correlation coefficient (r_pred²) is 0.728 for CoMFA and 0.805 for CoMSIA, which verifies that the model is predictable. Based on the potential maps of CoMFA and CoMSIA, a library containing a set of potent AChEi was designed. The inhibitory potential of the compounds in this library was found to be greater than the inhibitory potential of the most active compounds in the data set. The results obtained from this study laid the foundation for the development of effective drugs for AChEi.
- alzheimer's disease,
- 3D-QSAR,
- acetylcholinesterase inhibitor,
- 1,
- 2,
- 3-triazole-chromenone derivatives
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