Prolylisoxazoles: potent inhibitors of prolyloligopeptidase with antitrypanosomal activity

Gunther Bal; Pieter Van der Veken; Dimitri Antonov; Anne-Marie Lambeir; Philippe Grellier; Simon L Croft; Koen Augustyns; Achiel Haemers

doi:10.1016/s0960-894x(03)00579-1

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.

Authors

Gunther Bal¹, Pieter Van der Veken, Dimitri Antonov, Anne-Marie Lambeir, Philippe Grellier, Simon L Croft, Koen Augustyns, Achiel Haemers

Affiliation

¹ Department of Medicinal Chemistry, University of Antwerp, Belgium.

PMID: 14611847
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