Microbial and mammalian metabolism studies of the semisynthetic antimalarial, anhydrodihydroartemisinin

Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microb...

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Bibliographic Details
Published in:Pharmaceutical research 1994-07, Vol.11 (7), p.990-994
Main Authors: KHALIFA, S. I, BAKER, J. K, ROGERS, R. D, EL-FERALY, F. S, HUFFORD, C. D
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemistry
Antimalarials - metabolism
Antiparasitic agents
Artemisinins
Bacteria - metabolism
Biological and medical sciences
Chromatography, High Pressure Liquid
Crystallography, X-Ray
Fungi - metabolism
Magnetic Resonance Spectroscopy
Male
Medical sciences
Molecular Conformation
Pharmacology. Drug treatments
Rats
Rats, Wistar
Sesquiterpenes - chemistry
Sesquiterpenes - metabolism
Spectrometry, Mass, Fast Atom Bombardment
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Summary:Microbial metabolism studies of the semisynthetic antimalarial anhydrodihydroartemisinin (1), have shown that it is metabolized by a number of microorganisms. Large scale fermentation with Streptomyces lavendulae L-105 and Rhizopogon species (ATCC 36060) have resulted in the isolation of four microbial metabolites. These metabolites have been identified as a 14-carbon rearranged product (2), 9 beta-hydroxyanhydrodihydroartemisinin (3), 11-epi-deoxydihydroartemisinin (4), and 3 alpha-hydroxydeoxyanhydrodihydroartemisinin (5). Microbial metabolites were completely characterized by spectral methods, including 1H-NMR and 13C-NMR spectroscopy. The structure and stereochemistry of metabolite 2 were unequivocally established by X-ray crystallographic analysis. Thermospray mass spectroscopy/high-performance liquid chromatographic analyses of plasma from rats used in mammalian metabolism studies of 1 have shown microbial metabolite 3 to be the major mammalian metabolite. In vitro antimalarial testing has shown metabolite 3 to possess antimalarial activity.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1018979202933