Constrained peptidomimetics as antiplasmodial falcipain-2 inhibitors

Bioorg Med Chem. 2010 Jul 15;18(14):4928-38. doi: 10.1016/j.bmc.2010.06.010. Epub 2010 Jun 10.

Abstract

Herein we report the synthesis of a series of novel constrained peptidomimetics 2-10 endowed with a dipeptide backbone (D-Ser-Gly) and a vinyl ester warhead, structurally related to a previously identified lead compound 1, an irreversible inhibitor of falcipain-2, the main haemoglobinase of lethal malaria parasite Plasmodium falciparum. The new compounds were evaluated for their inhibition against falcipain-2, as well as against cultured P. falciparum. The inhibitory activity of the synthesized compounds was also evaluated against another protozoal cysteine protease, namely rhodesain of Trypanosoma brucei rhodesiense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology*
  • Cysteine Endopeptidases / metabolism*
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Peptides / chemistry*
  • Peptides / pharmacology*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology*
  • Trypanosoma brucei rhodesiense / drug effects
  • Trypanosoma brucei rhodesiense / enzymology
  • Trypanosomiasis, African / drug therapy

Substances

  • Antiprotozoal Agents
  • Peptides
  • Cysteine Endopeptidases
  • falcipain 2
  • rhodesain