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Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites. 2015
Ranae M Ranade, and
Zhongsheng Zhang, and
J Robert Gillespie, and
Sayaka Shibata, and
Christophe L M J Verlinde, and
Wim G J Hol, and
Erkang Fan, and
Frederick S Buckner
Department of Medicine, University of Washington, Seattle, Washington, USA.
The methionyl-tRNA synthetase (MetRS) is a novel drug target for the protozoan pathogen Giardia intestinalis. This protist contains a single MetRS that is distinct from the human cytoplasmic MetRS. A panel of MetRS inhibitors was tested against recombinant Giardia MetRS, Giardia trophozoites, and mammalian cell lines. The best compounds inhibited trophozoite growth at 500 nM (metronidazole did so at ∼5,000 nM) and had low cytotoxicity against mammalian cells, indicating excellent potential for further development as anti-Giardia drugs.
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