标题：A novel aminopeptidase N inhibitor developed by virtual screening approach
作者机构：[Feng, J] Shandong Analysis and Test Center, Shandong Academy of Sciences, Jinan, Shandong 250014, China, Department of Medicinal Chemistry, School of 更多
通讯作者地址：[Xu, WF]Shandong Univ, Sch Pharm, Dept Med Chem, Jinan 250012, Shandong, Peoples R China.
来源：Bioorganic and Medicinal Chemistry Letters
关键词：Aminopeptidase N inhibitors;Antitumor;Cell invasion;Docking;Virtual screening
摘要：A virtual screening was performed to discover novel lead structures as potent aminopeptidase N(APN) inhibitors. A commercial database containing about 1,60,000 molecules in SPECS was filtered by rule of five, zinc binding groups, pharmacophore models and binding pattern analysis. At last, 24 molecules were selected for enzyme inhibition assay and compound 2 exhibited the inhibition constant (Ki) of 2.79 ± 0.32 μM against APN compared with Bestatin (Ki= 3.37 ± 0.24 μM). Our results indicated that compound 2 exhibited good antiproliferative activities against a broad spectrum of human cancer cell lines, and induced cell cycle arrest at G1 phase and eventual apoptosis. Moreover, compound 2 can inhibit the invasion of MDA-MB-231 cells. In summary, our results suggest that compound 2, a potent APN inhibitor, is worthy of further development.