Malaria pigment and extracellular iron. Possible target for iron chelating agents

Biochemical Pharmacology
R L van ZylL McNamara

Abstract

Extracellular iron is necessary for many biochemical reactions involved in Plasmodium falciparum growth and multiplication. The incorporation of radioactive iron taken up by the parasite was found, electrophoretically and via gamma counting, to be mainly associated with the haemozoin only in the presence of the active metabolism of the parasite. The potent antimalarial activity of desferrioxamine, a ferric iron chelating agent, has shown that iron deprivation is inhibitory to the parasite. We propose that the mechanism of action of desferrioxamine in addition to the chelation of iron from the parasitic compartment, chelates iron from the haemozoin crystal resulting in free radical generation and parasite death. The ability of desferrioxamine and not the ferrous iron chelating agent, 2,2'-bipyridyl, to chelate the non-haem iron from the haemozoin structure indicates that the oxidative state of iron associated with the haemozoin structure is ferric in nature.

References

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Citations

Sep 1, 1994·Journal of Pharmacological and Toxicological Methods·E Hempelmann, H M Marques
Mar 2, 1999·Pharmacology & Therapeutics·G F MabezaG Weiss
Feb 22, 2013·Chemical Reviews·Paloma F SalasChris Orvig
Aug 17, 1999·Biochemical Pharmacology·S R VippaguntaJ L Vennerstrom
May 16, 2006·Medicinal Research Reviews·Suryanaryana VangapanduRahul Jain
Mar 9, 2007·Journal of Inorganic Biochemistry·Susan M ChemalyRobyn L van Zyl

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