title: Potentiation of the antimalarial agent rufigallol.
abstract: 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.
authors.affiliation: Medical Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon 97201, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Winter
authors.forename: K A
authors.initials: KA
authors.lastname: Cornell
authors.forename: L L
authors.initials: LL
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Ignatushchenko
authors.forename: D J
authors.initials: DJ
authors.lastname: Hinrichs
authors.forename: M K
authors.initials: MK
authors.lastname: Riscoe
mesh_terms: 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
chemical_list: D000880:Anthraquinones; D000962:Antimalarials; D001577:Benzophenones; D011619:Psychotropic Drugs; C052932:exifone; C103273:rufigallol