Prolylisoxazoles: potent inhibitors of prolyloligopeptidase with antitrypanosomal activity

Bioorg Med Chem Lett. 2003 Sep 1;13(17):2875-8. doi: 10.1016/s0960-894x(03)00579-1.

Abstract

Prolylprolylisoxazoles and prolylprolylisoxazolines were synthesized through a 1,3-dipolar cycloaddition reaction. These compounds are potent inhibitors of human and trypanosomal prolyloligopeptidase. They were shown to inhibit Trypanosoma cruzi and Trypanosoma b. brucei in in vitro systems with ED(50)'s in the lower microM range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Isoxazoles / chemical synthesis
  • Isoxazoles / pharmacology*
  • Prolyl Oligopeptidases
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / pharmacology*
  • Serine Endopeptidases / metabolism*
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / enzymology
  • Trypanosomatina / drug effects

Substances

  • Isoxazoles
  • Protease Inhibitors
  • Trypanocidal Agents
  • Serine Endopeptidases
  • PREPL protein, human
  • Prolyl Oligopeptidases