Assessment of antimalarial effect of ICL670A on in vitro cultures of Plasmodium falciparum.
We tested in vitro the antimalarial properties of ICL670A, a newly developed iron chelator for the long-term oral treatment of iron overload. Ring-stage synchronized cultures of Plasmodium falciparum cultured in human erythrocytes were exposed to different concentrations of ICL670A and the conventional iron chelator, desferrioxamine B (DFO), for 48 h. Malarial growth was measured by incorporation of [3H]-hypoxanthine. ICL670A at 30 micromol/l had marked antimalarial activity that was observable by 6 h after beginning the exposure of ring-stage parasites to the agent. Over 48 h of culture, malarial growth was significantly lower with ICL670A than with DFO at concentrations of both 30 micromol/l (P = 0.008) and 60 micromol/l (P = 0.001). At 48 h, growth relative to control was 53% with ICL670A and 83% with DFO at concentrations of 30 micromol/l, and 20% with ICL670A and 26% with DFO at concentrations of 60 micromol/l. Standard 50% inhibitory concentrations (IC50s) were similar for ICL670A and DFO. Precomplexation with iron completely abolished the inhibitory effect of ICL670A, indicating that this new agent, like DFO, probably inhibits parasite growth via deprivation of iron from critical targets within the parasite. Further studies to address the question of the antimalarial potential of ICL670A in combination with classic antimalarials would be of interest.
Goudeau
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C
Department of Microbiology, Howard University College of Medicine, 2121 Georgia Avenue NW, Washington, DC 20059, USA.
Loyevsky
M
M
Kassim
O O
OO
Gordeuk
V R
VR
Nick
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H
D000704:Analysis of Variance; D000818:Animals; D000962:Antimalarials; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D000077588:Deferasirox; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology*; D019271:Hypoxanthine / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D001565:Benzoates; D002614:Chelating Agents; D014230:Triazoles; D019271:Hypoxanthine; D003676:Deferoxamine; D000077588:Deferasirox