title: Molecular characteristics of carbaryl, a CYP1A1 gene inducer.
abstract: Carbaryl belongs to a series of compounds that activate the CYP1A1 gene. This study demonstrates the inability of carbaryl to compete with 2,3,7,8-tetrachlorodibenzo-p-dioxin for binding to the rat aryl hydrocarbon (dioxin) receptor. Structural and physicochemical properties of this insecticide, in relation to the requirements for binding to the aryl hydrocarbon receptor, are described. The crystal structure was determined experimentally using X-ray diffraction. A conformational search using molecular mechanics was performed by means of a Monte-Carlo-type method and a stochastic dynamics simulation. Lipophilicity calculations, log P, and molecular lipophilicity potential are also presented. Common and discriminating properties of carbaryl and aryl hydrocarbon receptor ligands are discussed.
authors.affiliation: UMR 5472 CNRS, Université de Bordeaux I, 351 Cours de la Libération, Talence Cedex, 33405, France.
authors.forename: C
authors.initials: C
authors.lastname: Sandoz
authors.forename: P
authors.initials: P
authors.lastname: Lesca
authors.forename: J F
authors.initials: JF
authors.lastname: Narbonne
authors.forename: A
authors.initials: A
authors.lastname: Carpy
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D012721:Carbaryl / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D007306:Insecticides; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D012721:Carbaryl