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

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 (IC50 = 3.1 μM) and 4l (IC50 = 5.2 μM) which exhibit similar potency to Bestatin (IC50 = 2.4 μM).