Studies on the in Vivo Biotransformation of the Tobacco Alkaloid β-Nicotyrine
| Autor: | Neal Castagnoli, Liu X, Kay Castagnoli, Van der Schyf Cj |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Insecticides Cytochrome Pyridines Stereochemistry Metabolite Toxicology Gas Chromatography-Mass Spectrometry Nicotine Mice chemistry.chemical_compound Biotransformation In vivo medicine Animals Chromatography High Pressure Liquid Pyrrole Mice Inbred ICR biology Autoxidation Alkaloid General Medicine Plants chemistry Biochemistry Inactivation Metabolic Microsomes Liver biology.protein Rabbits medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 13:336-341 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx990124t |
| Popis: | This paper reports the results of studies on the in vivo metabolic fate of the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine) in New Zealand white rabbits. Two previously characterized metabolites, 5-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (5-hydroxycotinine) and 2-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one, were present in low concentrations in the urine of the treated animals. The major urinary metabolite of beta-nicotyrine was identified as cis-3'-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (cis-3'-hydroxycotinine), the diastereoisomer of the major urinary metabolite of (S)-nicotine. The pathway leading to cis-3'-hydroxycotinine is proposed to proceed via autoxidation of 2-hydroxy-1-methyl-5-(3-pyridinyl)pyrrole, a postulated cytochrome P450-generated metabolite of beta-nicotyrine, followed by reduction of the carbon-carbon double bond present in the resulting 3-hydroxy-3-pyrrolin-2-one species. This proposal is supported by the in vivo biotransformation of 2-acetoxy-1-methyl-5-(3-pyridinyl)pyrrole, a latent form of the putative hydroxypyrrole intermediate, to cis-3'-hydroxycotinine. The in vivo conversion of 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one to 5-hydroxycotinine is offered as evidence that supports the proposed reduction step. |
| Databáze: | OpenAIRE |
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