Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives

被引：20

作者：

Liao, Sheng-Rong ^{[1
]}

Qin, Xiao-Chu ^{[2
,3
]}

Wang, Zhen ^{[2
,3
]}

Li, Ding ^{[4
]}

Xu, Liang ^{[5
]}

Li, Jin-Sheng ^{[1
]}

Tu, Zheng-Chao ^{[2
,3
]}

Liu, Yonghong ^{[1
]}

机构：

[1] Chinese Acad Sci, South China Sea Inst Oceanol, Res Ctr Marine Microbes, CAS Key Lab Trop Marine Bioresources & Ecol,Guang, Guangzhou 510301, Guangdong, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Mol Engn, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Lab Nat Prod Synth, Guangzhou 510530, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

[5] Enantiotech Corp Ltd, Zhongshan Torch Hitech, IndustrialDev Zone, Zhongshan 528437, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 121卷

关键词：

2,5-Diketopiperazine derivatives; Long alkyl chain; Cytotoxic activity; Apoptosis; Lipophilicity; PLASMINOGEN-ACTIVATOR INHIBITOR-1; MEDIATED MULTIDRUG-RESISTANCE; MEDICINAL CHEMISTRY; ANTITUMOR-ACTIVITY; P-GLYCOPROTEIN; IN-VITRO; PHENYLAHISTIN DERIVATIVES; TUBULIN-POLYMERIZATION; PLINABULIN NPI-2358; PIPERAFIZINE-A;

D O I：

10.1016/j.ejmech.2016.06.002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-1-monoallylated 2,5-diketopiperazine derivatives were designed, synthesized, and evaluated as cytotoxic agents against eight cancer cell lines by using CCK8 assay. These derivatives were substituted with methoxyphenyl groups at C-6 position, and various long alkyl side chains at C-3-position of the 2,5-diketopiperazine ring. The cytotoxic results showed that 4-methoxyphenyl group was better than 2-methoxyphenyl group as optimal substitutive group, while 3-methoxyphenyl group was not a suitable one. When the number (n value) of the methylene groups for the long alkyl side chain was 3 (compounds 1c and 3c), the derivatives had the strongest cytotoxicities. Compound 3c substituted with 4-methoxyphenyl group and pentylidene side chain exhibited strong activity (IC50 = 0.36-1.9 mu M) against all cancer cell lines, and could obviously induce apoptosis of cancer cell line U937 at 1.0 mu M after 48 h treatment. (C) 2016 Elsevier Masson SAS. All rights reserved.

引用

页码：500 / 509

页数：10

共 37 条

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