MALARIA PIGMENT AND EXTRACELLULAR IRON - POSSIBLE TARGET FOR IRON CHELATING-AGENTS

Extracellular iron is necessary for many biochemical reactions involve d in Plasmodium falciparum growth and multiplication. The incorporatio n of radioactive iron taken up by the parasite was found, electrophore tically and via gamma counting, to be mainly associated with the haemo zoin only in the presence of the active metabolism of the parasite. Th e potent antimalarial activity of desferrioxamine, a ferric iron chela ting agent, has shown that iron deprivation is inhibitory to the paras ite. We propose that the mechanism of action of desferrioxamine in add ition to the chelation of iron from the parasitic compartment, chelate s iron from the haemozoin crystal resulting in free radical generation and parasite death. The ability of desferrioxamine and not the ferrou s iron chelating agent, 2,2'-bipyridyl, to chelate the non-haem iron f rom the haemozoin structure indicates that the oxidative state of iron associated with the haemozoin structure is ferric in nature.