Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)

Bioorg Med Chem. 2013 May 1;21(9):2663-70. doi: 10.1016/j.bmc.2012.06.024. Epub 2012 Jun 19.

Abstract

Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC(50) = 0.074 ± 0.0026 μM) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Indoles
  • Protease Inhibitors
  • indoline-2,3-dione
  • CD13 Antigens