Quantitative structure-activity relationship studies of dibenzo[a,d]cycloalkenimine derivatives for non-competitive antagonists of N-methyl-d-aspartate based on density functional theory with electronic and topological descriptors

摘要

To establish a quantitative structure-activity relationship for non-competitive antagonists of the N-methyl-d-aspartate receptor, 48 substituted dibenzo[a,d]cycloalkenimine derivatives were analyzed by principal components, a descendant multiple regression analyses, multiple non-linear regression and an artificial neural network. We propose non-linear and linear quantitative structure-activity models and interpret the activity of the compounds by the multivariate statistical analysis. Density functional theory with Becke's three-parameter hybrid function and Lee-Yang-Parr exchange correlation functional calculations were performed to define the structure, chemical reactivity and properties of the study compounds. The topological and the electronic descriptors were computed with ACD/ChemSketch and Gaussian 03W programs, respectively. The study shows that multiple regression and multiple non-linear regression analyses predict activity; however, predictions made with a 6-2-1 artificial neural network model were more accurate. This model gave statistically significant results and showed good stability to data variation in leave-one-out cross-validation.