Novel L-arginine derivatives as aminopeptidase N inhibitors: design, chemistry, and pharmacological evaluation

Considering the important roles played in tumor, aminopeptidase N has been an appealing target for anti-tumor drug development. Here, a serial of novel aminopeptidase N inhibitors with L -arginine scaffold were designed, synthesized and evaluated for aminopeptidase N inhibitory activities. The preliminary anti-enzyme activity assay demonstrated that compounds 5e, 5h , 11e , 11g , and 11h showed comparable activities with the positive control bestatin, an approved aminopeptidase N inhibitor. In vitro anti-proliferation assay, compound 5f showed excellent activities against four kinds of tumor cells which overexpress aminopeptidase N. In vivo anti-metastasis assay, compounds 5f and 11g exhibited better activities than bestatin. So 5f and 11g should be lead compounds as novel aminopeptidase N inhibitors for further development.