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Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin
S I Khalifa1, J K Baker, M Jung
1Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University 38677, USA.
Purpose:
Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development.
Methods:
Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed.
Results:
Three microbial metabolites of deoxoartemisinin were identified (2, 3, and 4). Metabolite 3 was also found in rat plasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, and 4 as standards. All metabolites were thoroughly characterized by 1H and 13C-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin.
Conclusions:
Deoxoartemisinin was metabolized to three microbial metabolites. Metabolism by rats showed the presence of two metabolites in the plasma, one of which was the same as the microbial metabolite.