Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB

Bioorg Med Chem Lett. 2008 May 1;18(9):2883-5. doi: 10.1016/j.bmcl.2008.03.083. Epub 2008 Apr 8.


Human African trypanosomiasis (HAT) is caused by the protozoan parasite Trypanosoma brucei. The cysteine proteases of T. brucei have been shown to be crucial for parasite replication and represent an attractive point for therapeutic intervention. Herein we describe the synthesis of a series of thiosemicarbazones and their activity against the trypanosomal cathepsins TbcatB and rhodesain, as well as human cathepsins L and B. The activity of these compounds was determined against cultured T. brucei, and specificity was assessed with a panel of four mammalian cell lines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors
  • Cell Line
  • Cysteine Endopeptidases / drug effects*
  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemical synthesis
  • Thiosemicarbazones / pharmacology*
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosoma brucei brucei / enzymology


  • Cysteine Proteinase Inhibitors
  • Thiosemicarbazones
  • Trypanocidal Agents
  • Cathepsins
  • Cysteine Endopeptidases
  • rhodesain
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L