Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Giardia intestinalis Trophozoites | Zendy

Ranae M. Ranade | Zendy; Zhongsheng Zhang | Zendy; J. Robert Gillespie | Zendy; S. Shibata | Zendy; Christophe L. M. J. Verlinde | Zendy; Wim G. J. Hol | Zendy; Erkang Fan | Zendy; Frederick S. Buckner | Zendy

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Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Giardia intestinalis Trophozoites

Author(s) -

Ranae M. Ranade,

Zhongsheng Zhang,

J. Robert Gillespie,

S. Shibata,

Christophe L. M. J. Verlinde,

Wim G. J. Hol,

Erkang Fan,

Frederick S. Buckner

Publication year - 2015

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.01573-15

Subject(s) - giardia , biology , giardia lamblia , microbiology and biotechnology , recombinant dna , biochemistry , gene

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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