Design and Synthesis of Broad Spectrum Trypanosomatid Selective Inhibitors

A. L. Fraser, S. K. Menzies, E. F. B. King, L. B. Tulloch, E. R. Gould, M. K. Zacharova, T. K. Smith (Lead / Corresponding author), G. J. Florence (Lead / Corresponding author)

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Abstract

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.
Original languageEnglish
Pages (from-to)560-567
Number of pages8
JournalACS Infectious Diseases
Volume4
Issue number4
Early online date19 Jan 2018
DOIs
Publication statusPublished - 13 Apr 2018

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Keywords

  • Trypanosomatid
  • Natural Products
  • Drug Design
  • Chemical Tools
  • Photo-affinity

Cite this

Fraser, A. L., Menzies, S. K., King, E. F. B., Tulloch, L. B., Gould, E. R., Zacharova, M. K., Smith, T. K., & Florence, G. J. (2018). Design and Synthesis of Broad Spectrum Trypanosomatid Selective Inhibitors. ACS Infectious Diseases, 4(4), 560-567. https://doi.org/10.1021/acsinfecdis.7b00187