Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum.
- 1 October 1979
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 76 (10) , 5303-5307
- https://doi.org/10.1073/pnas.76.10.5303
Abstract
P. falciparum in culture grows optimally at 3% O2. Oxygen levels down to 0.5% still support growth, but anaerobic conditions do not. These findings, and the absence of the Krebs cycle in Plasmodium, suggested that in this organism O2 may not function in electron transport but rather may act through metalloprotein oxygenases. Tetraethylthiuram disulfide (Antabuse, disulfiram) and its reduction product diethyldithiocarbamate inhibit many metalloprotein oxygenases and have a lipid/H2O partition coefficient and high binding constant for metal ions, favoring selective toxicity to the malaria parasite. These compounds exhibited active antimalarial effects in vitro in concentrations down to 0.1 .mu.g/ml, the lowest level tested. Tetraethylthiuram disulfide at a level as low as 1 .mu.g/ml inhibited parasite glycolysis with no effect on glycolysis of normal erythrocytes. Erythrocytes pretreated with this drug at 10 .mu.g/ml did not support growth of the parasite.Keywords
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