Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites.
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.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Ranae M
RM
Ranade
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Zhongsheng
Z
Zhang
Department of Medicine, University of Washington, Seattle, Washington, USA.
J Robert
JR
Gillespie
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Sayaka
S
Shibata
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Christophe L M J
CL
Verlinde
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Wim G J
WG
Hol
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
Erkang
E
Fan
Department of Medicine, University of Washington, Seattle, Washington, USA fbuckner@uw.edu.
Frederick S
FS
Buckner
D000981:Antiprotozoal Agents / Q000494:pharmacology*; D016829:Giardia lamblia / Q000187:drug effects* / Q000201:enzymology; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008795:Metronidazole / Q000494:pharmacology; D053058:Trophozoites / Q000187:drug effects* / Q000201:enzymology
D000981:Antiprotozoal Agents; D008795:Metronidazole; D008718:Methionine-tRNA Ligase