Design, synthesis and biological evaluation of ferulic Acid amides as selective matrix metalloproteinase inhibitors

Med Chem. 2013 Nov;9(7):947-54. doi: 10.2174/1573406411309070008.

Abstract

A series of ferulic acid amides with extended P1' groups were synthesized and tested for their inhibitory activities on matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. Preliminary structure-activity relationship analysis and docking studies indicated that ferulic acid amides with electron-donating groups at the amino phenyl ring showed better inhibitory activities and selectivity than those with electron-withdrawing groups. Compound 3e, which had a hydroxyl group at meta-position of amino phenyl ring, showed considerable inhibitory activities against MMP-2, MMP-9 and best selectivity over MMP-1. The findings of this study would provide information for the exploitation and utilization of ferulic acid as MMP inhibitor for metastatic tumor treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Binding Sites
  • Coumaric Acids / chemical synthesis*
  • Coumaric Acids / chemistry
  • Coumaric Acids / pharmacology*
  • Enzyme Activation / drug effects
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase Inhibitors / chemical synthesis*
  • Matrix Metalloproteinase Inhibitors / chemistry
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinases / metabolism
  • Models, Molecular
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Amides
  • Coumaric Acids
  • Matrix Metalloproteinase Inhibitors
  • ferulic acid
  • Matrix Metalloproteinases