Journal article
In vitro metabolic transformations of vinblastine: oxidations catalyzed by human ceruloplasmin
Journal of medicinal chemistry, Vol.32(9), pp.2158-2162
09/01/1989
DOI: 10.1021/jm00129a023
PMID: 2769688
Abstract
The dimeric Vinca alkaloid vinblastine (VLB) undergoes metabolic transformation to three products in a reaction catalyzed by the human serum copper oxidase ceruloplasmin. The enzyme reaction requires chlorpromazine as a shuttle oxidant, and the course of the oxidation reaction appears to be subject to the nature of the shuttle oxidant used. Preparative-scale incubations have resulted in the isolation of three products, which were characterized by chemical and spectral analyses. The metabolites were identified as the ring fission product catharinine, obtained by oxidation of the Iboga ring system; an enamine/ether derivative obtained by oxidation of the Aspidosperma portion of VLB; and a metabolite embodying the same structural changes in both parts of the vinblastine dimeric structure. Catharinine is identical with the product of VLB oxidation obtained by peroxidase oxidation. The other two products are new metabolites and are derivatives of VLB. All of the metabolites are less active than VLB when tested in vitro vs the human T–cell leukemic cell line (CRFF-CEM). © 1989, American Chemical Society. All rights reserved.
Details
- Title: Subtitle
- In vitro metabolic transformations of vinblastine: oxidations catalyzed by human ceruloplasmin
- Creators
- Sayed A Elmarakby - University of IowaMichael W DuffelJohn P. N Rosazza
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.32(9), pp.2158-2162
- Publisher
- American Chemical Society
- DOI
- 10.1021/jm00129a023
- PMID
- 2769688
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Language
- English
- Date published
- 09/01/1989
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303285402771
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