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 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.
Khalifa
S I
SI
Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University 38677.
Baker
J K
JK
Rogers
R D
RD
el-Feraly
F S
FS
Hufford
C D
CD
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism*; D037621:Artemisinins; D001419:Bacteria / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D005658:Fungi / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C089918:anhydrodihydroartemisinin