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

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-triazolechromenone 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 Q(2) of the CoMFA model, the coefficient of non-cross-validation R-2, and the test value F are 0.597, 0.994, and 396.726, respectively. The cross-validation Q(2) of the CoMSIA model, the coefficient of the non-cross-validation R-2, and the test value F are 0.721, 0.979, and 131.107, respectively. The predictive correlation coefficient (r(pred)(2)) 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.