Artemisinins act through at least two targets in a yeast model

Moore, Catherine M., Hoey, Elizabeth M., Trudgett, Alan and Timson, David J. 2011. Artemisinins act through at least two targets in a yeast model. FEMS Yeast Research. 11 (2), pp. 233-237. https://doi.org/10.1111/j.1567-1364.2010.00706.x

TitleArtemisinins act through at least two targets in a yeast model
TypeJournal article
AuthorsMoore, Catherine M., Hoey, Elizabeth M., Trudgett, Alan and Timson, David J.
Abstract

Artemisinin and related compounds are potent and widely used antimalarial drugs but their biochemical mode of action is not clear. There is strong evidence that ATP-dependent calcium transporters are a key target in the malarial parasite. However, work using Saccharomyces cerevisiae suggests that disruption of mitochondrial function is critical in the cell killing activity of these compounds. Here it is shown that, in the absence of reducing agents, artemisinin and artesunate targeted the S. cerevisiae calcium channels Pmr1p and Pmc1p. Both compounds affected the growth of yeast on fermentable and nonfermentable media. This growth inhibition was not seen in a yeast strain in which the genes encoding both calcium channels were deleted. In the presence of reducing agents, which break the endoperoxide bridge in the drugs, growth inhibition was only observed in nonfermentable media. This inhibition could be partially relieved by the addition of a free radical scavenger. These results suggest that the drugs have two biochemical modes of action – one acting by specific binding to calcium channels and one involving free radical production in the mitochondria.

JournalFEMS Yeast Research
Journal citation11 (2), pp. 233-237
ISSN1567-1356
Year2011
PublisherOxford University Press
Digital Object Identifier (DOI)https://doi.org/10.1111/j.1567-1364.2010.00706.x
Web address (URL)https://doi.org/10.1111/j.1567-1364.2010.00706.x
Publication dates
Published in printMar 2011

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