Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers).
Six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against Plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of which are able to undergo iron(II)-mediated activation.
Dong
Yuxiang
Y
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Creek
Darren
D
Chollet
Jacques
J
Matile
Hugues
H
Charman
Susan A
SA
Wittlin
Sergio
S
Wood
James K
JK
Vennerstrom
Jonathan L
JL
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D004351:Drug Resistance; D020128:Inhibitory Concentration 50; D007501:Iron / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D045568:Tetraoxanes / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D010545:Peroxides; D045568:Tetraoxanes; D007501:Iron