Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain

Bioorg Med Chem Lett. 2005 Jan 3;15(1):121-3. doi: 10.1016/j.bmcl.2004.10.023.


Herein we report the synthesis and evaluation of a series of thiosemicarbazones as potential inhibitors of cysteine proteases relevant to parasitic diseases. Derivatives of thiosemicarbazone 1 were discovered to be potent inhibitors of cruzain and rhodesain, crucial proteases in the life cycles of Trypanosoma cruzi and T. brucei rhodesiense, the organisms causing Chagas' disease and sleeping sickness. However, the entire series had only modest potency against falcipain-2, an essential protease for Plasmodium falciparum, the organism causing malaria. Among the active inhibitors, several potently inhibited proliferation of cultures of T. brucei. However, only modest activity was observed in inhibition of proliferation of T. cruzi or P. falciparum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cysteine Endopeptidases / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Protozoan Proteins / antagonists & inhibitors*
  • Thiosemicarbazones / pharmacology*


  • Enzyme Inhibitors
  • Protozoan Proteins
  • Thiosemicarbazones
  • Cysteine Endopeptidases
  • cruzain, Trypanosoma cruzi
  • rhodesain