Background: Three dimensional quantitative structure activity relationship and pharmacophore modeling studied for tacrine derivatives as acetylcholinesterase inhibitors.
Methods: The three dimensional quantitative structure–activity relationship and pharmacophore methods were used to model the 68 derivatives of tacrine as human acetylcholinesterase inhibitors. The effect of the docked conformer of each molecule in the enzyme cavity was investigated on the predictive ability and statistical quality of the produced models.
Results: The whole data set was divided into two training and test sets using hierarchical clustering method. 3D-QSAR model, based on the comparative molecular field analysis has good statistical parameters as indicated by q2 =0.613, r2 =0.876, and r2pred =0.75. In the case of comparative molecular similarity index analysis, q2, r2 and r2pred values were 0.807, 0.96, and 0.865 respectively. The statistical parameters of the models proved that the inhibition data are well fitted and they have satisfactory predictive abilities.
Conclusion: The results from this study illustrate the reliability of using techniques in exploring the likely bonded conformations of the ligands in the active site of the protein target and improve the understanding over the structural and chemical features of AChE.