Design, synthesis and primary activity evaluation of L-arginine derivatives as amino-peptidase N/CD13 inhibitors

Jiajia Mou; Hao Fang; Fanbo Jing; Qiang Wang; Yingzi Liu; Huawei Zhu; Luqing Shang; Xuejian Wang; Wenfang Xu

doi:10.1016/j.bmc.2009.04.056

Design, synthesis and primary activity evaluation of L-arginine derivatives as amino-peptidase N/CD13 inhibitors

Bioorg Med Chem. 2009 Jul 1;17(13):4666-73. doi: 10.1016/j.bmc.2009.04.056. Epub 2009 May 3.

Authors

Jiajia Mou¹, Hao Fang, Fanbo Jing, Qiang Wang, Yingzi Liu, Huawei Zhu, Luqing Shang, Xuejian Wang, Wenfang Xu

Affiliation

¹ Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, PR China.

Abstract

A series of L-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compounds 5q and 5s (IC(50)=5.3 and 5.1 microM) showed similar inhibitory activities compared with bestatin (IC(50)=3.8 microM), which could be used as novel lead compounds for the future APN inhibitors development as anticancer agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Arginine / analogs & derivatives*
Arginine / chemical synthesis
Arginine / pharmacology*
CD13 Antigens / antagonists & inhibitors*
CD13 Antigens / metabolism*
Humans
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase Inhibitors*
Microsomes, Liver / enzymology
Models, Molecular
Molecular Structure
Protein Binding
Structure-Activity Relationship
Swine

Substances

Antineoplastic Agents
Matrix Metalloproteinase Inhibitors
Arginine
CD13 Antigens
Matrix Metalloproteinase 2