甲硫氨酰 - tRNA合成酶抑制剂对肠贾第鞭毛虫滋养体具有强大的活性。
Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites.
作者信息
Ranade Ranae M, Zhang Zhongsheng, Gillespie J Robert, Shibata Sayaka, Verlinde Christophe L M J, Hol Wim G J, Fan Erkang, Buckner Frederick S
机构信息
Department of Medicine, University of Washington, Seattle, Washington, USA.
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
出版信息
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.
摘要
甲硫氨酰 - tRNA合成酶（MetRS）是原生动物病原体肠道贾第虫的一种新型药物靶点。这种原生生物含有一种与人类细胞质MetRS不同的单一MetRS。一组MetRS抑制剂针对重组贾第虫MetRS、贾第虫滋养体和哺乳动物细胞系进行了测试。最佳化合物在500 nM时抑制滋养体生长（甲硝唑在约5000 nM时才起作用），并且对哺乳动物细胞具有低细胞毒性，这表明其作为抗贾第虫药物具有进一步开发的巨大潜力。
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