Threonine peptidases as drug targets against malaria

Expert Opin Ther Targets. 2011 Apr;15(4):365-78. doi: 10.1517/14728222.2011.555399. Epub 2011 Feb 1.

Abstract

Introduction: Malaria is caused by the intracellular parasite Plasmodium falciparum. Although numerous therapies are available to fight the disease, the number of pharmacophores is small, and constant development of novel therapies, especially with new targets, is desirable to fight developing resistance against presently prescribed drugs.

Areas covered: This review discusses research on plasmodial threonine peptidases along with recent advances in proteasome inhibitor development.

Expert opinion: While PfHslV is an attractive drug target in malaria, more investigation is required to clarify its functional role in the parasite. More efforts should also be invested in assessing the plasmodial proteasome as a drug target. The few papers investigating the effect of proteasome inhibitors on different stages of the life cycle point towards important roles not only during asexual, but also in hepatic and sexual stages, in humans and the mosquito. If this holds true, this is a key argument to further develop proteasome inhibitors for use against malaria.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimalarials / chemistry
  • Antimalarials / pharmacokinetics
  • Antimalarials / therapeutic use*
  • Culicidae
  • Female
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Male
  • Molecular Sequence Data
  • Molecular Targeted Therapy
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology
  • Plasmodium falciparum / growth & development
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / therapeutic use*
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Threonine / chemistry
  • Threonine / pharmacokinetics
  • Threonine / therapeutic use*

Substances

  • Antimalarials
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Threonine
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex