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

Antimicrob Agents Chemother. 2015 Nov;59(11):7128-31. doi: 10.1128/AAC.01573-15. Epub 2015 Aug 31.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiprotozoal Agents / pharmacology*
  • Giardia lamblia / drug effects*
  • Giardia lamblia / enzymology
  • Methionine-tRNA Ligase / antagonists & inhibitors*
  • Metronidazole / pharmacology
  • Trophozoites / drug effects*
  • Trophozoites / enzymology

Substances

  • Antiprotozoal Agents
  • Metronidazole
  • Methionine-tRNA Ligase

Associated data

  • PDB/4EG5