Malaria pigment and extracellular iron. Possible target for iron chelating agents.
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.
van Zyl
R L
RL
Department of Experimental and Clinical Pharmacology, University of the Witwatersrand, Medical School, Johannesburg, South Africa.
Havlik
I
I
Hempelmann
E
E
MacPhail
A P
AP
McNamara
L
L
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry; D007501:Iron / Q000032:analysis*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010860:Pigments, Biological / Q000032:analysis*; D010963:Plasmodium falciparum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
D000962:Antimalarials; D005290:Ferric Compounds; D006420:Hemeproteins; D007502:Iron Chelating Agents; D010860:Pigments, Biological; C020753:hemozoin; D015082:2,2'-Dipyridyl; D007501:Iron; D003676:Deferoxamine