Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation

Chunhua Ma; Jiangying Cao; Xuewu Liang; Yongxue Huang; Ping Wu; Yingxia Li; Wenfang Xu; Yingjie Zhang

doi:10.1016/j.ejmech.2015.11.021

Novel leucine ureido derivatives as aminopeptidase N inhibitors. Design, synthesis and activity evaluation

Eur J Med Chem. 2016 Jan 27:108:21-27. doi: 10.1016/j.ejmech.2015.11.021. Epub 2015 Nov 26.

Authors

Chunhua Ma¹, Jiangying Cao², Xuewu Liang², Yongxue Huang², Ping Wu³, Yingxia Li³, Wenfang Xu², Yingjie Zhang⁴

Affiliations

¹ School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China; School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
² School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
³ School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
⁴ School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address: zhangyingjie@sdu.edu.cn.

PMID: 26629857
DOI: 10.1016/j.ejmech.2015.11.021

Abstract

Aminopeptidase N (APN/CD13) over-expressed on tumor cells and tumor microenvironment, plays critical roles in tumor invasion, metastasis and angiogenesis. Here we described the design, synthesis and preliminary activity studies of novel leucine ureido derivatives as aminopeptidase N (APN/CD13) inhibitors. The results showed that compound 7a had the most potent inhibitory activity against APN with the IC50 value of 20 nM, which could be used for further anticancer agent research.

Keywords: Aminopeptidase N; Inhibitors; Leucine ureido derivatives; Synthesis.

Publication types

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

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
CD13 Antigens / antagonists & inhibitors*
CD13 Antigens / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Leucine / analogs & derivatives*
Leucine / pharmacology
Liver Neoplasms / drug therapy
Liver Neoplasms / enzymology
Liver Neoplasms / pathology
Lung Neoplasms / drug therapy
Lung Neoplasms / enzymology
Lung Neoplasms / pathology
Lung Neoplasms / secondary
Mice
Molecular Structure
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / enzymology
Neoplasms, Experimental / pathology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Enzyme Inhibitors
CD13 Antigens
Leucine