Document Detail


Conceptual DFT properties-based 3D QSAR: analysis of inhibitors of the nicotine metabolizing CYP2A6 enzyme.
MedLine Citation:
PMID:  19090569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sofie Van Damme; Patrick Bultinck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of computational chemistry     Volume:  30     ISSN:  1096-987X     ISO Abbreviation:  J Comput Chem     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-01     Completed Date:  2009-11-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9878362     Medline TA:  J Comput Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1749-57     Citation Subset:  IM    
Copyright Information:
Copyright 2008 Wiley Periodicals, Inc.
Affiliation:
Department of Inorganic and Physical Chemistry, Ghent University, Krijgslaan 281 S-3, B-9000 Gent, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*,  metabolism*
Coumarins / metabolism
Enzyme Inhibitors / chemistry*,  pharmacology*
Humans
Imidazoles / metabolism
Models, Chemical
Models, Molecular
Nicotine / analogs & derivatives*,  pharmacology
Protein Binding
Quantitative Structure-Activity Relationship*
Quantum Theory
Chemical
Reg. No./Substance:
0/Coumarins; 0/Enzyme Inhibitors; 0/Imidazoles; 0/coumarin 7; 54-11-5/Nicotine; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/coumarin 7-hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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