Novel potent 2,5-pyrrolidinedione peptidomimetics as aminopeptidase N inhibitors. Design, synthesis and activity evaluation

Bioorg Med Chem Lett. 2012 Jan 15;22(2):850-3. doi: 10.1016/j.bmcl.2011.12.048. Epub 2011 Dec 16.

Abstract

A series of novel aminopeptidase N inhibitors with 2,5-pyrrolidinedione scaffold were chemically synthesized. Their preliminary biological activities in enzyme kinetics and cell assay in vitro and anti-metastasis profile in vivo were also evaluated. The results indicated that all the compounds displayed potent inhibitory activity against aminopeptidase N. Compound 8f inhibited aminopeptidase N activity with IC(50) value of 1.0μM and displayed better activity profile in vivo than that of bestatin.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Peptidomimetics / chemical synthesis
  • Peptidomimetics / chemistry
  • Peptidomimetics / pharmacology*
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / chemical synthesis
  • Phenylalanine / chemistry
  • Phenylalanine / pharmacology
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Succinimides / chemical synthesis
  • Succinimides / chemistry
  • Succinimides / pharmacology*

Substances

  • 2-amino-N-(1-(2-(hydroxyamino)-2-oxoethyl)-2,5-dioxopyrrolidin-3-yl)-3-phenylpropanamide
  • Antineoplastic Agents
  • Peptidomimetics
  • Protease Inhibitors
  • Succinimides
  • Phenylalanine
  • CD13 Antigens