OXIDATION OF VINCRISTINE CATALYZED BY PEROXIDASE AND CERULOPLASMIN

The dimeric Catharanthus alkaloid vincristine (1) is oxidized to the s ame ring fission product in incubations with either horseradish peroxi dase or the human serum copper oxidase ceruloplasmin. Horseradish pero xidase-catalyzed oxidation of vincristine requires hydrogen peroxide, whereas ceruloplasmin-catalyzed oxiation of vincristine requires chlor promazine as a ''shuttle oxidant''. Preparative-scale incubations allo wed for the production, isolation, structural characterization, and bi ological evaluation of the metabolite. The metabolite was identified a s the heterocyclic ring cleavage product N-formylcatharinine (5). N-Fo rmylcatharinine was 118 times less active than vincristine in an in vi tro test against a human T-cell leukemic cell line. Therefore, these e nzyme-catalyzed reactions lead to bioinactivation of vincristine.