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  • Title: Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides.
    Author: Vennerstrom JL, Fu HN, Ellis WY, Ager AL, Wood JK, Andersen SL, Gerena L, Milhous WK.
    Journal: J Med Chem; 1992 Aug 07; 35(16):3023-7. PubMed ID: 1501229.
    Abstract:
    Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50's comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.
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