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 (IC(50)=3.1microM) and 4l (IC(50)=5.2microM) which exhibit similar potency to Bestatin (IC(50)=2.4microM).
Li
Qianbin
Q
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China.
Fang
Hao
H
Xu
Wenfang
W
D000081:Acetamides / Q000737:chemistry; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000081:Acetamides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C030686:acetamide; D018826:CD13 Antigens; D020782:Matrix Metalloproteinases