Medicinal Chemistry Research

, Volume 26, Issue 11, pp 3015–3025 | Cite as

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

  • Jiajia MouEmail author
  • Yepeng Luan
  • Danghui Chen
  • Qiang Wang
Original Research


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.


L-arginine derivatives Aminopeptidase N Synthesis Anti-enzyme activity Anti-proliferation activity Anti-metastasis activity 



This work was supported by National Nature Science Foundation of China (Grant No. 21502142) and Tianjin Research Program of Application Foundation and Advanced Technology (No.15JCQNJC14100) and Program for Changjiang Scholars and Innovative Research Team in University (IRT_14R41). The authors thank South-central University for Nationalities for supporting of CADD softwares.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Jiajia Mou
    • 1
    Email author
  • Yepeng Luan
    • 2
  • Danghui Chen
    • 1
  • Qiang Wang
    • 3
  1. 1.Department of Medicinal ChemistrySchool of Chinese Materia Medica, Tianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.Department of Medicinal ChemistryCollege of Pharmacy, Qingdao UniversityQingdaoChina
  3. 3.College of PharmacySouth-central University for NationalitiesWuhanChina

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