Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes

Bioorg Med Chem Lett. 2008 Jan 15;18(2):624-8. doi: 10.1016/j.bmcl.2007.11.070. Epub 2007 Nov 22.


A systematic study of P2 and P3 substitution in a series of vinyl sulfone cysteine protease inhibitors is described. The introduction of a methyl substituent in the P2 phenylalanine aryl ring had a favorable effect on protease inhibition and conferred modest selectivity for rhodesain over cruzain. Rhodesain selectivity could be enhanced further by combining these P2 modifications with certain P3 amide substituents.

Publication types

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

MeSH terms

  • Animals
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Ethylenes / chemistry*
  • Ethylenes / pharmacology*
  • Structure-Activity Relationship
  • Sulfonic Acids / chemistry*
  • Sulfonic Acids / pharmacology*
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma / drug effects*
  • Trypanosoma / enzymology


  • Cysteine Proteinase Inhibitors
  • Ethylenes
  • Sulfonic Acids
  • Trypanocidal Agents
  • ethylenesulfonic acid