Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides.
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had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data.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.
Vennerstrom
J L
JL
College of Pharmacy, University of Nebraska Medical Center, Omaha 68198-6025.
Fu
H N
HN
Ellis
W Y
WY
Ager
A L
AL
Wood
J K
JK
Andersen
S L
SL
Gerena
L
L
Milhous
W K
WK
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D005027:Ethylene Oxide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D010545:Peroxides; D013141:Spiro Compounds; D005027:Ethylene Oxide