Potentiation of an antimalarial oxidant drug

R. W. Winter, Marina Ignatushchenko, Olumide A T Ogundahunsi, Kenneth A. Cornell, Ayoade M J Oduola, David J. Hinrichs, Michael Riscoe

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

In a previous report we described the synergistic antimalarial interaction between two structurally similar compounds, rufigallol and exifone. To explain this phenomenon, we proposed that exifone is transformed inside the parasitized erythrocyte into a xanthone with potent antimalarial properties. We speculated that the transformation process was induced by the prooxidant activity of rufigallol. On the basis of this model we hypothesized that exifone would act synergistically with other oxidant drugs. In the present study we have found a similar synergistic interaction between exifone and ascorbic acid (vitamin C) against both chloroquine-susceptible and multidrug-resistant strains of Plasmodium falciparum. The prooxidant activity of ascorbic acid against Plasmodium-infected erythrocytes is believed to result from an intraerythrocytic Fenton reaction occurring in the acidic food vacuole of the parasite. The hydroxyl radicals produced during this process are believed to attack exifone, which undergoes cyclodehydration to become 2,3,4,5,6-pentahydroxyxanthone (XS). Evidence presented to support this 'xanthone hypothesis' includes the demonstration that the exifone → X5 transformation occurs readily in vitro under mildly acidic conditions in the presence of iron, ascorbic acid, and oxygen.

Original languageEnglish (US)
Pages (from-to)1449-1454
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume41
Issue number7
StatePublished - Jul 1997

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Antimalarials
Oxidants
Ascorbic Acid
Erythrocytes
Plasmodium
Chloroquine
Plasmodium falciparum
Vacuoles
Hydroxyl Radical
exifone
Parasites
Iron
Oxygen
Food
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Winter, R. W., Ignatushchenko, M., Ogundahunsi, O. A. T., Cornell, K. A., Oduola, A. M. J., Hinrichs, D. J., & Riscoe, M. (1997). Potentiation of an antimalarial oxidant drug. Antimicrobial Agents and Chemotherapy, 41(7), 1449-1454.

Potentiation of an antimalarial oxidant drug. / Winter, R. W.; Ignatushchenko, Marina; Ogundahunsi, Olumide A T; Cornell, Kenneth A.; Oduola, Ayoade M J; Hinrichs, David J.; Riscoe, Michael.

In: Antimicrobial Agents and Chemotherapy, Vol. 41, No. 7, 07.1997, p. 1449-1454.

Research output: Contribution to journalArticle

Winter, RW, Ignatushchenko, M, Ogundahunsi, OAT, Cornell, KA, Oduola, AMJ, Hinrichs, DJ & Riscoe, M 1997, 'Potentiation of an antimalarial oxidant drug', Antimicrobial Agents and Chemotherapy, vol. 41, no. 7, pp. 1449-1454.
Winter RW, Ignatushchenko M, Ogundahunsi OAT, Cornell KA, Oduola AMJ, Hinrichs DJ et al. Potentiation of an antimalarial oxidant drug. Antimicrobial Agents and Chemotherapy. 1997 Jul;41(7):1449-1454.
Winter, R. W. ; Ignatushchenko, Marina ; Ogundahunsi, Olumide A T ; Cornell, Kenneth A. ; Oduola, Ayoade M J ; Hinrichs, David J. ; Riscoe, Michael. / Potentiation of an antimalarial oxidant drug. In: Antimicrobial Agents and Chemotherapy. 1997 ; Vol. 41, No. 7. pp. 1449-1454.
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