Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26).
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Haim N, Roman J, Nemec J, Sinha BK
Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26).
Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20.
- PubMed ID
- 3006680 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Etoposide Prostaglandin G/H synthase 1 Protein Humans UnknownSubstrateDetails Etoposide Prostaglandin G/H synthase 2 Protein Humans UnknownSubstrateDetails