Novel 3-galloylamido-N'-substituted-2,6-piperidinedione-N-acetamide peptidomimetics as metalloproteinase inhibitors

Bioorg Med Chem Lett. 2007 May 15;17(10):2935-8. doi: 10.1016/j.bmcl.2006.12.095. Epub 2007 Jan 5.

Abstract

Both of aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential metallopeptidases in the development of tumor invasion and angiogenesis. Novel potent peptidomimetic inhibitors, containing 3-galloylamido-N'-substituted-2,6-piperidinedione-N-acetamide, have been designed and synthesized according to the conformational constraint strategy. The preliminary biological test showed that most of the compounds displayed high inhibitory activity against MMP-2 and low activity against APN except compounds 6 (IC(50)=3.1microM) and 4l (IC(50)=5.2microM) which exhibit similar potency to Bestatin (IC(50)=2.4microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry
  • CD13 Antigens / antagonists & inhibitors*
  • CD13 Antigens / chemistry
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / chemistry
  • Matrix Metalloproteinases / metabolism
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • acetamide
  • CD13 Antigens
  • Matrix Metalloproteinases