Synthesis and structure-activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1206-11. doi: 10.1016/j.bmcl.2013.01.027. Epub 2013 Jan 16.


Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure-activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Caffeic Acids / chemical synthesis
  • Caffeic Acids / chemistry*
  • Caffeic Acids / pharmacology*
  • Humans
  • Matrix Metalloproteinase Inhibitors / chemical synthesis
  • Matrix Metalloproteinase Inhibitors / chemistry*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Amides
  • Caffeic Acids
  • Matrix Metalloproteinase Inhibitors
  • caffeic acid