Potentiation of the antimalarial agent rufigallol

• DOI: 10.1128/aac.40.6.1408
• Publication Date: 2018-10-09T00:25:38Z
• Authors: R W Winter; K A Cornell; L L Johnson; M Ignatushchenko; D J Hinrichs; M K Riscoe
• Keywords: Psychotropic Drugs; Erythrocytes; Plasmodium falciparum; Anthraquinones; Drug Synergism; 3. Good health; Antimalarials; Benzophenones; Structure-Activity Relationship; 03 medical and health sciences; 0302 clinical medicine; Animals

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.