Novel Aminopeptidase N Inhibitors with Improved Antitumor Activities

被引：4

作者：

Wang, Qiang ^{[1
,2
]}

Shi, Qiao

Huang, Lu ^{[3
]}

机构：

[1] Georgia State Univ, Dept Chem, Ctr Diagnost & Therapeut, Atlanta, GA 30302 USA

[2] Georgia State Univ, Ctr Biotechnol & Drug Design, Atlanta, GA 30302 USA

[3] BGI Wuhan Pharmaceut Co Ltd, Wuhan 430075, Hubei Province, Peoples R China

来源：

LETTERS IN DRUG DESIGN & DISCOVERY | 2016年 / 13卷 / 01期

关键词：

Aminopeptidase N; inhibitor; structural modification; L-lysine based; docking; TUMOR-CELL INVASION; CD13; PROLIFERATION; ANGIOGENESIS; SUPPRESSES;

D O I：

10.2174/1570180812666150611190608

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of aminopeptidase N (APN) inhibitors were designed and synthesized. Enzyme inhibitory, docking and antiproliferative studies were performed to evaluate the derived molecules. Molecule D15, with IC50 values of 10.9 mu M, showed the best performance in the APN enzymatic inhibition assay. The binding pattern of molecule D9 and D15 in the active site of APN was predicted by docking studies. Hydrophobic and H-bond interactions were discovered to make key roles in the ligand-receptor bindings. Compared with the previous C7, several molecules such as D9, D14 and D15, exhibited significantly improved activities in inhibiting the growth of HL-60, ES-2, A549 and PLC cell lines.

引用

页码：98 / 106

页数：9

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