Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds.
Drug Metab Dispos
; 24(2): 203-10, 1996 Feb.
Article
en En
| MEDLINE
| ID: mdl-8742232
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.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Sistema Enzimático del Citocromo P-450
/
Hidrocarburos Clorados
/
Isoenzimas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Drug Metab Dispos
Asunto de la revista:
FARMACOLOGIA
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos