| Title: | Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds |
| Author(s): | Waller CL; Evans MV; McKinney JD; |
| Address: | "Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA" |
| ISSN/ISBN: | 0090-9556 (Print) 0090-9556 (Linking) |
| Abstract: | "Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, has been used to analyze the metabolic rates, as intrinsic clearance, of a series of chlorinated volatile organic compounds (VOCs). A comparison between 3D-QSAR and conventional Hansch-type QSAR is provided. To develop predictive 3D-QSARs for metabolism, the standard CoMFA model based on steric and electrostatic potential fields must be supplemented with hydropathic and molecular orbital information also in the form of three-dimensional fields. A mechanistic interpretation of chlorinated VOC metabolism by cytochrome P450 isozymes is provided as a rationalization for the inclusion of multiple fields in the CoMFA 3D-QSAR model. Models of this type have practical utility in the development of generalized physiologically-based pharmacokinetic models, as well as the rational, structure-based, design and/or selection of compounds for use in the in vivo and in vitro metabolic studies" |
| Keywords: | "Cytochrome P-450 Enzyme System/*metabolism Electrochemistry Hydrocarbons, Chlorinated/*metabolism Isoenzymes/*metabolism Kinetics Models, Molecular Structure-Activity Relationship Volatilization;" |
| Notes: | "MedlineWaller, C L Evans, M V McKinney, J D eng 1996/02/01 Drug Metab Dispos. 1996 Feb; 24(2):203-10" |
