Biomimetic metabolism of artelinic acid by chemical cytochrome P-450 model systems

• Published in: Pharmaceutical research 1997-10, Vol.14 (10), p.1449-1454
• Main Authors: IDOWU, O. R, LIN, A. J, GRACE, J. M, PEGGINS, J. O
• Format: Article
• Language: English
• Subjects: Acids; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemistry; Antimalarials - metabolism; Antiparasitic agents; Artemisinins; Benzoates - chemistry; Biological and medical sciences; Chromatography; Chromatography, High Pressure Liquid; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; Ferrous Compounds - chemistry; General pharmacology; Hemin - chemistry; Malaria; Mass Spectrometry; Medical sciences; Metabolism; Metabolites; Nitrogen; Oxyquinoline - chemistry; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Sesquiterpenes - chemistry; Sesquiterpenes - metabolism; Solvents; Spectrum analysis; Sulfhydryl Compounds - chemistry; Thimerosal; Yeast
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1012185124972

To study the reaction of artelinic acid with chemical model systems of cytochrome P-450 as a means of obtaining authentic samples of the putative metabolites necessary for identification of the mammalian metabolites of artelinic acid. Artelinic acid was reacted with different organic complexes of iron(II). The reaction products were isolated and characterized by NMR and thermospray mass spectroscopy. Five compounds which are putative metabolites of artelinic acid were isolated from these reactions and unambiguously identified, while the identity of two other compounds await final confirmation. Standards of possible metabolites of artelinic acid can be produced by the reaction of the compound with ferrous complexes that may simulate cytochrome P-450 catalyzed metabolism of xenobiotics. This approach may provide a simple and versatile method for the formation of metabolites of artemisinin compounds which is more advantageous than previous approaches with fungal-based systems.