Elmarakby S A, Duffel M W, Goswami A, Sariaslani F S, Rosazza J P
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
J Med Chem. 1989 Mar;32(3):674-9. doi: 10.1021/jm00123a030.
Vinblastine is converted to a single major metabolite during in vitro enzymatic oxidations catalyzed by horseradish peroxidase in the presence of hydrogen peroxide. Preparative-scale enzyme incubation permitted the isolation of sufficient amount of the transformation product for complete structural identification and biological evaluation. The metabolite was identified as catharinine (also known as vinamidine) by 1H and 13C NMR and by mass spectrometry. Incubations conducted in H2(18)O-enriched water gave catharinine in which a single atom of 18O was incorporated into the metabolite structure. The labeling experiment provided evidence for an unusual ring-fission pathway by which peroxidase transforms vinblastine to catharinine. Catharinine is 77 times less active than vinblastine when tested in vitro against the human T-cell leukemic cell line (CRFF-CEM).
