Synthesis and evaluation of non-peptidic cysteine protease inhibitors of P. falciparum derived from etacrynic acid

Molecules. 2008 Dec 23;14(1):19-35. doi: 10.3390/molecules14010019.

Abstract

A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC(50) values of 9.0 and 18.8 microM against Plasmodia.

Publication types

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

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Cysteine Endopeptidases / drug effects*
  • Cysteine Endopeptidases / genetics
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Ethacrynic Acid / analogs & derivatives*
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics

Substances

  • Antimalarials
  • Cysteine Proteinase Inhibitors
  • Recombinant Proteins
  • Cysteine Endopeptidases
  • falcipain 2
  • falcipain 3
  • Ethacrynic Acid