Journal article
Metabolism of the Catharanthus Alkaloids: from Streptomyces griseus to Monoamine Oxidase B
Journal of natural products (Washington, D.C.), Vol.55(3), pp.269-284
03/01/1992
DOI: 10.1021/np50081a001
PMID: 1593278
Abstract
More than three decades after their discovery and implementation in medicine, essentially nothing is known about the metabolism or the implications of metabolism in mechanism of action or toxicity of the Catharanthus alkaloids. The frustrating paucity of information about pathways of metabolism has limited a major source of structure-activity relationship information and has blocked a critical avenue necessary for the logical development of new and more useful Catharanthus alkaloids. Microbial transformations, peroxidases, copper oxidases, mouse and rat cytochrome P-450 systems, and mouse brain and bovine liver monoamine oxidase (MAO) preparations have been explored in the study of Catharanthus alkaloid metabolism. In this report, we present results which have clarified the involvement of enzymatic and chemically catalyzed one-electron oxidations that yield nitrogen-centered cation radicals, iminium, and carbinolamine intermediates, all of which explain how new carbon-carbon and carbon-oxygen bonds form, or break and rearrange. The dimeric Catharanthus alkaloids are recalcitrant to oxidations catalyzed by monoamine oxidases and to both normal and induced P-450 rat microsomal preparations. However, the Catharanthus alkaloids appear to be selective reversible inhibitors of MAO-B. Chemical and biochemical aspects of the metabolic transformations of dimeric Catharanthus alkaloids are reviewed together with the implications of our findings. © 1992, American Chemical Society. All rights reserved.
Details
- Title: Subtitle
- Metabolism of the Catharanthus Alkaloids: from Streptomyces griseus to Monoamine Oxidase B
- Creators
- John P. N Rosazza - University of IowaMichael W DuffelSayed El-MarakbySung Ho Ahn
- Resource Type
- Journal article
- Publication Details
- Journal of natural products (Washington, D.C.), Vol.55(3), pp.269-284
- DOI
- 10.1021/np50081a001
- PMID
- 1593278
- NLM abbreviation
- J Nat Prod
- ISSN
- 0163-3864
- eISSN
- 1520-6025
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 03/01/1992
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303286902771
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