Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum

J Med Chem. 2013 Jun 27;56(12):5213-7. doi: 10.1021/jm4005972. Epub 2013 Jun 13.

Abstract

The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry*
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology*
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / chemistry
  • Catalytic Domain
  • Chemistry Techniques, Synthetic
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Models, Molecular
  • Phosphorous Acids / chemistry*
  • Plasmodium falciparum / enzymology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Phosphorous Acids
  • phosphonic acid
  • Arginine
  • CD13 Antigens

Associated data

  • PDB/4K3N
  • PDB/4K5L
  • PDB/4K5M
  • PDB/4K5N
  • PDB/4K5O
  • PDB/4K5P