Potentiation of the antimalarial agent rufigallol

R. W. Winter, Kenneth A. Cornell, Linda L. Johnson, Marina Ignatushchenko, David J. Hinrichs, Michael Riscoe

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 ~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.

Original languageEnglish (US)
Pages (from-to)1408-1411
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number6
StatePublished - Jun 1996

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Chloroquine
Antimalarials
Reactive Oxygen Species
Drug Synergism
Erythrocytes
Trophozoites
Plasmodium falciparum
Parasites
Clone Cells
rufigallol
exifone
xanthone

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Winter, R. W., Cornell, K. A., Johnson, L. L., Ignatushchenko, M., Hinrichs, D. J., & Riscoe, M. (1996). Potentiation of the antimalarial agent rufigallol. Antimicrobial Agents and Chemotherapy, 40(6), 1408-1411.

Potentiation of the antimalarial agent rufigallol. / Winter, R. W.; Cornell, Kenneth A.; Johnson, Linda L.; Ignatushchenko, Marina; Hinrichs, David J.; Riscoe, Michael.

In: Antimicrobial Agents and Chemotherapy, Vol. 40, No. 6, 06.1996, p. 1408-1411.

Research output: Contribution to journalArticle

Winter, RW, Cornell, KA, Johnson, LL, Ignatushchenko, M, Hinrichs, DJ & Riscoe, M 1996, 'Potentiation of the antimalarial agent rufigallol', Antimicrobial Agents and Chemotherapy, vol. 40, no. 6, pp. 1408-1411.
Winter RW, Cornell KA, Johnson LL, Ignatushchenko M, Hinrichs DJ, Riscoe M. Potentiation of the antimalarial agent rufigallol. Antimicrobial Agents and Chemotherapy. 1996 Jun;40(6):1408-1411.
Winter, R. W. ; Cornell, Kenneth A. ; Johnson, Linda L. ; Ignatushchenko, Marina ; Hinrichs, David J. ; Riscoe, Michael. / Potentiation of the antimalarial agent rufigallol. In: Antimicrobial Agents and Chemotherapy. 1996 ; Vol. 40, No. 6. pp. 1408-1411.
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