Activity of diphenyl ether benzyl amines against Human African Trypanosomiasis

James P. Hagen, Grant Darner, Samuel Anderson, Katie Higgins, Derek A. Leas, Ananya Mitra, Victoria Mashinson, Tasloach Wol, Carlos Vera-Esquivel, Bret Belter, Monica Cal, Marcel Kaiser, Alexander Wallick, Rosalie C. Warner, Paul H. Davis

Research output: Contribution to journalArticle

Abstract

Insect-borne parasite Trypanosoma brucei plagues humans and other animals, eliciting the disease Human African trypanosomiasis, also known as African sleeping sickness. This disease poses the biggest threat to the people in Sub-Saharan Africa. Given the high toxicity and difficulties with administration of currently available drugs, a novel treatment is needed. Building on known Human African trypanosomiasis structure–activity relationship (SAR), we now describe a number of functionally simple diphenyl ether analogs which give low micromolar activity (IC50 = 0.16–0.96 μM) against T. b. rhodesiense. The best compound shows favorable selectivity against the L6 cell line (SI = 750) and even greater selectivity (SI = 1200) against four human cell lines. The data herein provides direction for the ongoing optimization of antitrypanosomal diphenyl ethers.

Original languageEnglish (US)
Article number103590
JournalBioorganic Chemistry
Volume97
DOIs
StatePublished - Apr 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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    Hagen, J. P., Darner, G., Anderson, S., Higgins, K., Leas, D. A., Mitra, A., Mashinson, V., Wol, T., Vera-Esquivel, C., Belter, B., Cal, M., Kaiser, M., Wallick, A., Warner, R. C., & Davis, P. H. (2020). Activity of diphenyl ether benzyl amines against Human African Trypanosomiasis. Bioorganic Chemistry, 97, [103590]. https://doi.org/10.1016/j.bioorg.2020.103590