Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of VP16-213. Identification of a new metabolite.
VP16 was submitted to oxidation catalyzed by horseradish peroxidase (HRP) and H2O2 in phosphate buffer (pH 7.0). The product of the reaction, which has a high performance liquid chromatographic (HPLC) retention time different from the previously known metabolites of VP16, was identified as 1,2,3,4-tetradehydro-VP16 by 1H-NMR and mass spectrometry (MS) analysis. It was found to result from the loss of four hydrogens and the formation of an aromatic ring (ring C of VP16). This new product retains, in the 4' position of the E ring of VP16, the hydroxy group which is crucial for the antitumoral activity of podophyllotoxin derivatives. The reaction was linear in a wide range of VP16 concentrations and was dependent on the concomitant presence of peroxidase and H2O2.
D000107:Acetylation; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D005047:Etoposide / Q000378:metabolism*; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D011034:Podophyllotoxin / Q000031:analogs & derivatives*
D005609:Free Radicals; D005047:Etoposide; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D010544:Peroxidases; D011034:Podophyllotoxin