Fenton's oxidation: a tool for the investigation of potential drug metabolites

Abstract

Within the scope of searching for new lead structures in the field of anti-infectives, we ascertained Fenton's reagent to be an easy-to-handle and non-expensive tool for screening the metabolic profile of new bioactive compounds. The underlying chemistry of the Fenton's one-electron oxidation is comparable to that of cytochrome P450, which is the main metabolism enzyme. To study the metabolic screening capability, we subjected different antibiotics and the antiplasmodial naphthylisoquinoline alkaloid dioncophylline A to Fenton's reagent and examined the obtained compound libraries by liquid chromatography/tandem mass spectrometry (LC-MS/MS). For ciprofloxacin and linezolid about half of literature-known metabolites were identified as products of Fenton's oxidation. For dioncophylline A six new possible metabolites were discovered.