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
收藏
页码：500 / 509
页数：10
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