Potentiation of the antimalarial agent rufigallol.
We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar analysis was approximately 60-fold for experiments initiated with asynchronous parasites. The most pronounced synergism was observed in experiments with synchronized trophozoite-infected erythrocytes, in which the degree of synergy was at least 300-fold. While the mechanism underlying this drug potentiation remains unresolved, it is hypothesized that rufigallol acts in pro-oxidant fashion to produce oxygen radicals inside parasitized erythrocytes. These radicals would attack exifone, thereby initiating its transformation into a more potent compound, a xanthone.
Winter
R W
RW
Medical Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon 97201, USA.
Cornell
K A
KA
Johnson
L L
LL
Ignatushchenko
M
M
Hinrichs
D J
DJ
Riscoe
M K
MK
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D001577:Benzophenones / Q000494:pharmacology*; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000880:Anthraquinones; D000962:Antimalarials; D001577:Benzophenones; D011619:Psychotropic Drugs; C052932:exifone; C103273:rufigallol