Fraser Andrew L, Menzies Stefanie K, King Elizabeth F B, Tulloch Lindsay B, Gould Eoin R, Zacharova Marija K, Smith Terry K, Florence Gordon J
EaStCHEM School of Chemistry and School of Biology, Biomedical Sciences Research Complex , University of St Andrews , North Haugh, St Andrews , KY16 9ST , United Kingdom.
ACS Infect Dis. 2018 Apr 13;4(4):560-567. doi: 10.1021/acsinfecdis.7b00187. Epub 2018 Jan 19.
Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern that have a devastating effect on the developing world due to their burden on human and animal health. In this work, we detail the preparation of a focused library of substituted-tetrahydropyran derivatives and their evaluation as selective chemical tools for trypanosomatid inhibition and the follow-on development of photoaffinity probes capable of labeling target protein(s) in vitro. Several of these functionalized compounds maintain low micromolar activity against Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, and Leishmania donovani. In addition, we demonstrate the utility of the photoaffinity probes for target identification through preliminary cellular localization studies.
由寄生虫感染引起的被忽视热带病一直以来都是且日益受到关注，因其对人类和动物健康造成负担，对发展中世界产生了毁灭性影响。在这项工作中，我们详细阐述了一个取代四氢吡喃衍生物聚焦文库的制备过程，以及将其作为用于抑制锥虫的选择性化学工具和后续开发能够在体外标记靶蛋白的光亲和探针的评估过程。其中几种功能化化合物对布氏锥虫、克氏锥虫、硕大利什曼原虫和杜氏利什曼原虫保持低微摩尔活性。此外，我们通过初步的细胞定位研究证明了光亲和探针在靶标鉴定中的实用性。
