Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma brucei

Zachary B. MacKey, Arthur M. Baca, Jeremy P. Mallari, Beth Apsel, Anang Shelat, Elizabeth J. Hansell, Peter K. Chiang, Brian Wolff, Kiplin R. Guy, Janice Williams, James H. McKerrow

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Chemotherapy against human African trypanosomiasis relies on four drugs that cause frequent and occasionally severe side-effects. Because human African trypanosomiasis is a disease of poor people in Africa, the traditional market-driven pathways to drug development are not available. One potentially rapid and cost-effective approach to identifying and developing new trypanocidal drugs would be high throughput-screening of existing drugs already approved for other uses, as well as clinical candidates in late development. We have developed an ATP-bioluminescence assay that could be used to rapidly and efficiently screen compound libraries against trypanosomes in a high throughput-screening format to validate this notion. We screened a collection of 2160 FDA-approved drugs, bioactive compounds and natural products to identify hits that were cytotoxic to cultured Trypanosoma brucei at a concentration of 1 μm or less. This meant that any hit identified would be effective at a concentration readily achievable by standard drug dosing in humans. From the screen, 35 hits from seven different drug categories were identified. These included the two approved trypanocidal drugs, suramin and pentamidine, several other drugs suspected but never validated as trypanocidal, and 17 novel trypanocidal drugs.

Original languageEnglish
Pages (from-to)355-363
Number of pages9
JournalChemical Biology and Drug Design
Issue number5
StatePublished - May 2006


  • Biological screening
  • FDA
  • Natural products
  • Trypanosoma brucei

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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