Journal of Medicinal Chemistry
Dispiro-l,2,4,5tetraoxanes2 -4 were synthesized as potential peroxide a n t h a l a* d 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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data Moreover, artemisinin (1) and 4 had equivalent ED”s against P. berghei in vivo in the multiple-dose Thompson tat; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-l,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-l,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.
Vennerstrom, Jonathan L.; Fu, Hong-Ning; Walter Reed Army Institute of Research; Ager, Arba L. Jr.; Wood, James K.; Walter Reed Army Institute of Research; Walter Reed Army Institute of Research; and Walter Reed Army Institute of Research, "Dispiro- 1,2,4,5-tetraoxanes: A New Class of Antimalarial Peroxides" (1992). Chemistry Faculty Publications. 19.