Abstract
The melaminophenyl arsenical melarsoprol is the main drug used against late-stage sleeping sickness caused by Trypanosoma brucei subspecies. Its active metabolite in the human body is melarsen oxide. Here, it is shown that this metabolite inhibits growth of the fission yeast Schizosaccharomyces pombe and that its toxicity can be abolished efficiently by thiamine (vitamin B(1)), thiamine analogues, and the pyrimidine moiety of the thiamine molecule. Uptake of melarsen oxide is mediated by a membrane protein (car1p), which is involved in the uptake of thiamine and its pyrimidine moiety. Melarsoprol is taken up by cells in a thiamine- and car1p-dependent manner but is not toxic to cells.
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