Journal article
Oxidations of Vincristine Catalyzed by Peroxidase and Ceruloplasmin
Journal of natural products (Washington, D.C.), Vol.60(11), pp.1125-1129
11/01/1997
DOI: 10.1021/np970226o
PMID: 9392881
Abstract
The dimeric Catharanthus alkaloid vincristine (1) is oxidized to the same ring fission product in incubations with either horseradish peroxidase or the human serum copper oxidase ceruloplasmin. Horseradish peroxidase- catalyzed oxidation of vincristine requires hydrogen peroxide, whereas ceruloplasmin-catalyzed oxiation of vincristine requires chlorpromazine as a 'shuttle oxidant'. Preparative-scale incubations allowed for the production, isolation, structural characterization, and biological evaluation of the metabolite. The metabolite was identified as the heterocyclic ring cleavage product N-formylcatharinine (5). N-Formylcatharinine was 118 times less active than vincristine in an in vitro test against a human T-cell leukemic cell line. Therefore, these enzyme-catalyzed reactions lead to bioinactivation of vincristine.
Details
- Title: Subtitle
- Oxidations of Vincristine Catalyzed by Peroxidase and Ceruloplasmin
- Creators
- Sung Ho Ahn - University of IowaMichael W. Duffel - University of IowaJohn P. N. Rosazza - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of natural products (Washington, D.C.), Vol.60(11), pp.1125-1129
- DOI
- 10.1021/np970226o
- PMID
- 9392881
- ISSN
- 0163-3864
- eISSN
- 1520-6025
- Language
- English
- Date published
- 11/01/1997
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303162202771
Metrics
10 Record Views