TY - JOUR
T1 - Iron chelators as antimalarials
T2 - The biochemical basis of selective cytotoxicity
AU - Cabantchik, Z. I.
PY - 1995
Y1 - 1995
N2 - 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 cirulating 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 as in the clinic. Z. Ioav 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.
AB - 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 cirulating 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 as in the clinic. Z. Ioav 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.
UR - http://www.scopus.com/inward/record.url?scp=0028859989&partnerID=8YFLogxK
U2 - 10.1016/0169-4758(95)80123-5
DO - 10.1016/0169-4758(95)80123-5
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AN - SCOPUS:0028859989
SN - 0169-4758
VL - 11
SP - 74
EP - 78
JO - Parasitology Today
JF - Parasitology Today
IS - 2
ER -