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

Pharm Res. 1997 Oct;14(10):1449-54. doi: 10.1023/a:1012185124972.

Abstract

Purpose: 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.

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / metabolism*
  • Artemisinins*
  • Benzoates / chemistry
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism*
  • Ferrous Compounds / chemistry
  • Hemin / chemistry
  • Mass Spectrometry
  • Oxyquinoline / chemistry
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / metabolism*
  • Sulfhydryl Compounds / chemistry
  • Thimerosal

Substances

  • Antimalarials
  • Artemisinins
  • Benzoates
  • Ferrous Compounds
  • Sesquiterpenes
  • Sulfhydryl Compounds
  • artelinic acid
  • 2-thiosalicylic acid
  • Thimerosal
  • Oxyquinoline
  • Hemin
  • Cytochrome P-450 Enzyme System