Iron chelators: mode of action as antimalarials

Acta Haematologica
Z I CabantchikA Tsafack

Abstract

Malaria parasites growing inside human erythrocytes 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 synergisti...Continue Reading

Citations

Apr 6, 1999·Pharmacology & Therapeutics·P L Olliaro, Y Yuthavong
Mar 2, 1999·Pharmacology & Therapeutics·G F MabezaG Weiss
Mar 5, 2003·Molecular and Biochemical Parasitology·Mark LoyevskyTracey A Rouault
Jul 21, 1999·Molecular and Biochemical Parasitology·M LoyevskyV R Gordeuk
Feb 18, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·N S PostmaG Storm
Feb 15, 2002·British Journal of Haematology·C GoudeauH Nick
May 23, 2002·Antimicrobial Agents and Chemotherapy·Andrea RothenederGünter Weiss
Sep 19, 2000·Infection and Immunity·O OlakanmiL S Schlesinger
Nov 26, 2004·The Journal of Parasitology·José-Antonio F RobledoGerardo R Vasta
Apr 25, 2006·The Journal of Parasitology·Jacob GolenserPeter Kremsner
Feb 14, 2004·Redox Report : Communications in Free Radical Research·Jacob GolenserAdrian Luty
Jun 1, 2000·Experimental Parasitology·E DeharoV R Gordeuk
Feb 16, 2008·Hemoglobin·Joannes J M MarxNiki A Georgiou
Sep 22, 2009·Drug Metabolism Reviews·Eugene D Weinberg, Jym Moon
May 23, 2007·Insect Biochemistry and Molecular Biology·Jesús Martínez-BarnetcheHumberto Lanz-Mendoza
Nov 15, 2011·EMBO Reports·Sílvia PortugalMaria M Mota
Aug 15, 1997·Biochemical Pharmacology·M LoyevskyV Gordeuk
Jul 30, 2014·Frontiers in Pharmacology·Carlos Penha-GonçalvesLuciana V de Moraes
May 17, 2014·Frontiers in Pharmacology·Martha A ClarkCarla Cerami
Aug 17, 1999·Biochemical Pharmacology·S R VippaguntaJ L Vennerstrom
Sep 1, 1996·Antimicrobial Agents and Chemotherapy·A TsafackZ I Cabantchik
Jul 29, 2021·Malaria Journal·Patrick B Memvanga, Christian I Nkanga

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.