Design and synthesis of broad spectrum trypanosomatid selective inhibitors
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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 photo-affinity probes capable of labeling target protein(s) in vitro. Several of these functionalised compounds maintain low micromolar activity against Trypanosoma brucei, Trypanosoma cruzi, Leishmania major and Leishmania donovani. In addition we demonstrate the utility of the photo-affinity probes for target identification through preliminary cellular localization studies.
Fraser , A L , Menzies , S K , King , E F B , Tulloch , L , Gould , E R , Zacharova , M , Smith , T K & Florence , G J 2018 , ' Design and synthesis of broad spectrum trypanosomatid selective inhibitors ' ACS Infectious Diseases , vol. 4 , no. 4 , pp. 560-567 . https://doi.org/10.1021/acsinfecdis.7b00187
ACS Infectious Diseases
Copyright © 2018 American Chemical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1021/acsinfecdis.7b00187
DescriptionThis work was funded by the Leverhulme Trust (GJF) and the European Community’s Seventh Framework Programme under grant agreement No. 602773 [Project KINDRED] (TKS).
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