Characterization of the Major Metabolite of Sampangine in Rats

Sampangine (1) is a plant-derived antifungal copyrine alkaloid extracted from the stem bark of Cananga odorata. Although it possesses potent in vitro antifungal activity, 1 is devoid of significant and reproducible in vivo activity in a mouse model of cryptococcosis. Speculating that the lack of in...

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Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2000-05, Vol.63 (5), p.685-687
Main Authors: Orabi, Khaled Y, Walker, Larry A, Clark, Alice M, Hufford, Charles D
Format: Article
Language:English
Subjects:
Alkaloids - pharmacokinetics
Alkaloids - pharmacology
Animals
Antifungal Agents - pharmacokinetics
Antifungal Agents - pharmacology
Bacteria - drug effects
Biotransformation
Cananga odorata
Chromatography, High Pressure Liquid
Cryptococcosis - drug therapy
Cryptococcus neoformans
Cryptococcus neoformans - drug effects
Glucuronides
Heterocyclic Compounds, 4 or More Rings
Magnetic Resonance Spectroscopy
Male
Mass Spectrometry
Mice
Microbial Sensitivity Tests
Rats
Rats, Wistar
SAM MM1
sampangine
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Summary:Sampangine (1) is a plant-derived antifungal copyrine alkaloid extracted from the stem bark of Cananga odorata. Although it possesses potent in vitro antifungal activity, 1 is devoid of significant and reproducible in vivo activity in a mouse model of cryptococcosis. Speculating that the lack of in vivo activity could be due to metabolism, a study was undertaken to begin to develop an understanding of the pharmacokinetics, and particularly metabolism of 1. Following intraperitoneal administration of 1 to rats, urine was collected, extracted, and chromatographed over a reversed-phase C18 silica column to yield the major metabolite, SAM MM1 (2), which was identified by NMR and MS to be an O-glucuronide conjugate of sampangine. In addition, two other unstable, structurally uncharacterized minor metabolites were produced, as evidenced by HPLC analysis. Evaluation of the antifungal and antibacterial activities of 2 showed it to have remarkable in vitro activity against Cryptococcus neoformans.
ISSN:0163-3864
1520-6025
DOI:10.1021/np990552z