Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity

Bioorg Med Chem Lett. 2001 Mar 26;11(6):761-4. doi: 10.1016/s0960-894x(01)00055-5.

Abstract

Malaria continues to represent a very serious health problem in the tropics. The current methods of clinical treatment are showing deficiencies due to the increased incidence of resistance in the parasite. In the present paper we report the design, synthesis, and evaluation of potential antimalarial agents against a novel target, protein farnesyltransferase. We show that the most potent compounds are active against Plasmodium falciparum in vitro at submicromolar concentrations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Drug Design
  • Drug Resistance
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Enzyme Inhibitors
  • FTI-2277
  • Imidazoles
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase