Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3527-30. doi: 10.1016/s0960-894x(03)00756-x.


While commercial isatins were practically inactive against the target proteases, thiosemicarbazone derivatives were found to be active. The most active compound from the series displayed an inhibitory IC(50) value of 1 microM against rhodesain. One thiosemicarbazone was found to be active against all three proteases with inhibitory IC(50) values of 10 microM or less. A combination of N-benzylation and appropriate substitution on the aromatic portion of the isatin scaffold was generally found to be beneficial especially against cruzain for ketone inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Evaluation, Preclinical
  • Isatin / chemical synthesis*
  • Isatin / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacology*
  • Spectrometry, Mass, Fast Atom Bombardment
  • Thiosemicarbazones / chemical synthesis*
  • Thiosemicarbazones / pharmacology*


  • Protease Inhibitors
  • Thiosemicarbazones
  • Isatin