Li Qianbin, Fang Hao, Xu Wenfang
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China.
Bioorg Med Chem Lett. 2007 May 15;17(10):2935-8. doi: 10.1016/j.bmcl.2006.12.095. Epub 2007 Jan 5.
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).
氨肽酶N（APN）和基质金属蛋白酶（MMP）都是肿瘤侵袭和血管生成过程中必不可少的金属肽酶。根据构象限制策略，设计并合成了含有3-没食子酰氨基-N'-取代-2,6-哌啶二酮-N-乙酰胺的新型强效拟肽抑制剂。初步生物学试验表明，除化合物6（IC50 = 3.1μM）和4l（IC50 = 5.2μM）对APN和MMP-2显示出与贝抑素（IC50 = 2.4μM）相似的抑制活性外，大多数化合物对MMP-2表现出高抑制活性，对APN表现出低活性。
