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Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites.

ABSTRACT: 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.

SUBMITTER: Ranade RM

PROVIDER: S-EPMC4604383 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites.

Ranade Ranae M RM Zhang Zhongsheng Z Gillespie J Robert JR Shibata Sayaka S Verlinde Christophe L M J CL Hol Wim G J WG Fan Erkang E Buckner Frederick S FS

Antimicrobial agents and chemotherapy 20150831 11

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 f ...[more]

PMID: 26324270

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