Conceptual DFT properties-based 3D QSAR : analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme

Structure-activity relationships of 46 P450 2A6 inhibitors were analyzed using the 3D-QSAR methodology. The analysis was carried out to confront the use of traditional steric and electrostatic fields with that of a number of fields reflecting conceptual DFT properties: electron density, HOMO. LUMO, and Fukui f(-) function as 3D fields. The most predictive models were obtained by combining file information of the electron density with the Fukui f(-) function (r(2) = 0.82, q(2) = 0.72), yielding it statistically significant and predictive model. The generated model was able to predict the inhibition potencies of all external test set of live chemicals. The result of the analysis indicates that conceptual DFT-based molecular fields can be useful as 3D QSAR molecular interaction fields