Synthesis and molecular simulation study of furoic peptidomimetic derivatives as potent aminopeptodase N inhibitors

Pharmazie. 2018 Mar 5;73(3):123-127. doi: 10.1691/2018.7911.

Abstract

The aminopeptidase N (APN) plays a critical role in angiogenesis and is over-expressed in tumor cells. In this paper, we report the synthesis and enzyme inhibition assay of furoic peptidomimetic compounds. These new compounds exhibit potent inhibitory ability toward APN with IC50 values lying in the micromolar level. The binding mode of inhibitors in APN active site was explained by a molecular simulation study. These data reveal that ligand coordinating with the catalytic Zn-ion is very important for inhibitory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • CD13 Antigens / antagonists & inhibitors*
  • Catalytic Domain / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Indicators and Reagents
  • Ligands
  • Models, Molecular
  • Molecular Docking Simulation
  • Peptidomimetics / chemical synthesis*
  • Peptidomimetics / pharmacology*
  • Protein Binding
  • Structure-Activity Relationship
  • Swine
  • Zinc / chemistry

Substances

  • Enzyme Inhibitors
  • Indicators and Reagents
  • Ligands
  • Peptidomimetics
  • CD13 Antigens
  • Zinc