IRON CHELATORS AS ANTIMALARIALS - THE BIOCHEMICAL BASIS OF SELECTIVE CYTOTOXICITY

Like all living organisms, malaria parasites need iron for vital cell functions and must handle their cellular contents in a highly regulated fashion. However, in the asexual stage of growth, parasites present a special case of iron metabolism. Despite dwelling in a sea of hemoglobin and carrying inside the remnants of its degradation products, intracellular parasites have no obvious means for mobilizing bioavailable iron from the host or from the medium. In that sense they differ from most mammalian cells which are exposed to body fluids and acquire the metal from circulating iron carriers. The uniqueness of iron handling by parasites is manifested in their susceptibility to drug-induced deprivation of the metal. Both natural and synthetic iron(III) chelators of the hydroxamate family have been shown to abolish cell growth in vitro, and to reduce malaria infection in vivo as well os in the clinic. Z. loav Cabantchik here explores the molecular basis for the selective cytotoxicity of iron(III) hydroxamate chelators and the potential of iron chelation therapy in the management of malaria.