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


METHODS
Artelinic acid was reacted with different organic complexes of iron(II). The reaction products were isolated and characterized by NMR and thermospray mass spectroscopy.


RESULTS
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.


CONCLUSIONS
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.
Idowu
O R
OR
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100, USA. Dr._Remi_Idowu@wrsmtp-ccmail.army.mil
Lin
A J
AJ
Grace
J M
JM
Peggins
J O
JO
D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism*; D037621:Artemisinins; D001565:Benzoates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005296:Ferrous Compounds / Q000737:chemistry; D006427:Hemin / Q000737:chemistry; D013058:Mass Spectrometry; D015125:Oxyquinoline / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013849:Thimerosal
D000962:Antimalarials; D037621:Artemisinins; D001565:Benzoates; D005296:Ferrous Compounds; D012717:Sesquiterpenes; D013438:Sulfhydryl Compounds; C062768:artelinic acid; C026196:2-thiosalicylic acid; D013849:Thimerosal; D015125:Oxyquinoline; D006427:Hemin; D003577:Cytochrome P-450 Enzyme System