Chemical and Enzymatic Oxidation of Furosemide: Formation of Pyridinium Salts
| Autor: | Ling-Jen Chen, Leo T. Burka |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Spectrometry Mass Electrospray Ionization Magnetic Resonance Spectroscopy Metabolite Carboxylic acid Pyridinium Compounds Toxicology Aldehyde chemistry.chemical_compound Cytochrome P-450 Enzyme System Nucleophile Furosemide medicine Animals Organic chemistry Dimethyldioxirane Diuretics Biotransformation Chromatography High Pressure Liquid chemistry.chemical_classification Molecular Structure Chemistry General Medicine Rats Inbred F344 Rats Microsomes Liver Epoxy Compounds Salts Pyridinium Oxidation-Reduction Enone medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 20:1741-1744 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx700262z |
| Popis: | Furosemide (Lasix) is frequently used in the treatment of cardiovascular and renal disease. Only one metabolite, furosemide glucuronide, has ever been identified. Oxidation of furosemide by cytochrome P450 has been demonstrated, but the metabolite(s) has never been identified. The oxidation of furosemide by dimethyldioxirane in acetone and by liver microsomal incubations was explored in this study. The first observable product from dimethyldioxirane oxidation was a ring-expanded enone resulting from an intramolecular condensation of the aldehyde group of the enonal, the secondary amine, and the carboxylic acid in a Mannich-like reaction. Keto-enol tautomerization and opening of the lactone gave a stable pyridinium salt. The pyridinium salt was also observed in the microsomal incubations of furosemide. The presence of an internal nucleophile in furosemide may have a significant effect on the toxicology and possibly the pharmacology of this furan. |
| Databáze: | OpenAIRE |
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