Iron Chelators: Mode of Action as Antimalarials

Z. Ioav Cabantchik*, Hava Glickstein, Jacob Golenser, Mark Loyevsky, Appolinaire Tsafack

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Malaria parasites growing inside human eryhtrocytes differ from mammalian cells in their mode of acquisition of bioavailable iron and in their susceptibility to the antiproliferative action of iron chelators. We have assessed here three major properties associated with these phenomena: (a) the stage-dependent nature of parasite iron mobilization from the host and its integration into parasite proteins; (b) the differential permeability of the plasma membrane to iron chelators, and (c) the in situ generation of toxic chelator-metal complexes in the intracellular milieu of infected cells. We have used a combination of synthetic and natural iron chelators with similar iron-binding properties but markedly different capacities to permeate membranes. The profiles of action of these agents on the in vitro growth of Plasmodium falciparum were assessed in terms of inhibitory concentrations, speed of action, stage dependence and reversibility of effects. These profiles provided the basis for a working model of chelator action on parasitized cells. The model allowed us to predict major improvements in the antimalarial performance of iron chelators when used in appropriate combinations of slow- and fast-permeating substances. The synergistic actions found in vitro for various combinations of iron chelators are in accordance with the model and have implications for the design of therapeutic schemes.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalActa Haematologica
Volume95
Issue number1
DOIs
StatePublished - 1 Jan 1996

Keywords

  • Chelators
  • Chemotherapy
  • Iron
  • Malaria
  • Plasmodiumfalciparum

Fingerprint

Dive into the research topics of 'Iron Chelators: Mode of Action as Antimalarials'. Together they form a unique fingerprint.

Cite this