Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26).
The peroxidative activation of the antitumor drugs, etoposide (VP-16) and teniposide (VM-26), has been studied in vitro. Both of these drugs, in the presence of horseradish peroxidase or prostaglandin synthetase, formed phenoxy radical intermediates. Furthermore, this activation also resulted in the formation of two metabolites from each of the drugs. Using HPLC and mass spectrometry, one of the metabolites was shown to be the reactive o-quinone derivative of the parent drug which resulted from the peroxidative O-demethylation. It appears that O-demethylation catalyzed by peroxidases may be an important mechanism for the formation of reactive intermediates and may play a role in the mechanism of action of VP-16 and VM-26.
D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D005047:Etoposide; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000378:metabolism; D013058:Mass Spectrometry; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D010545:Peroxides; D011034:Podophyllotoxin / Q000031:analogs & derivatives; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011809:Quinones; D013713:Teniposide
D005609:Free Radicals; D010545:Peroxides; D011809:Quinones; D005047:Etoposide; D013713:Teniposide; D010090:Oxidoreductases, O-Demethylating; D006735:Horseradish Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases; D011034:Podophyllotoxin