Design, Synthesis and Biological Evaluation of Caffeic Acid Amides as Selective MMP-2 and MMP-9 Inhibitors

Strategy, Management and Health Policy Preclinical Research A series of caffeic acid amides with extended P1' groups were synthesized and tested for their inhibitory activities on matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. Compound 3f showed considerable inhibitory activities against MMP-2, MMP-9, and best selectivity over MMP-1. Preliminary structureactivity relationship analysis and docking studies indicated that caffeic acid amides with electron-donating groups at p-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups. The findings of this study would provide information for the exploitation and utilization of caffeic acid as MMP inhibitor for metastatic tumor treatment.