title: Conceptual DFT properties-based 3D QSAR: analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme.
abstract: 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 the information of the electron density with the Fukui f- function (r2 = 0.82, q2 = 0.72), yielding a statistically significant and predictive model. The generated model was able to predict the inhibition potencies of an external test set of five chemicals. The result of the analysis indicates that conceptual DFT-based molecular fields can be useful as 3D QSAR molecular interaction fields.
authors.affiliation: Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 S-3, B-9000 Gent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Van Damme
authors.forename: Patrick
authors.initials: P
authors.lastname: Bultinck
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003374:Coumarins / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D007093:Imidazoles; C517283:coumarin 7; D009538:Nicotine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6