TY - JOUR
T1 - Dispiro-1,2,4,5-tetraoxanes
T2 - A New Class of Antimalarial Peroxides
AU - Vennerstrom, Jonathan L.
AU - Fu, Hong Ling
AU - Ellis, William Y.
AU - Andersen, Steven L.
AU - Gerena, Lucia
AU - Ager, Arba L.
AU - Wood, James K.
PY - 1992/8/1
Y1 - 1992/8/1
N2 - 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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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.
AB - 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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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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U2 - 10.1021/jm00094a015
DO - 10.1021/jm00094a015
M3 - Article
C2 - 1501229
AN - SCOPUS:0026746330
SN - 0022-2623
VL - 35
SP - 3023
EP - 3027
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 16
ER -