2. Academic Validation
  3. Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives

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

  • Eur J Med Chem. 2016 Oct 4:121:500-509. doi: 10.1016/j.ejmech.2016.06.002.
Sheng-Rong Liao 1,  Xiao-Chu Qin 2,  Zhen Wang 2,  Ding Li 3,  Liang Xu 4,  Jin-Sheng Li 1,  Zheng-Chao Tu 2,  Yonghong Liu 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • 2 Laboratory of Molecular Engineering and Laboratory of Natural Product Synthesis, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • 3 School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
  • 4 Enantiotech Corp., Ltd., Zhongshan Torch Hi-Tech, IndustrialDevelopment Zone, Zhongshan 528437, China.
  • 5 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Research Center for Marine Microbes, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. Electronic address: yonghongliu@scsio.ac.cn.
PMID: 27318124 DOI: 10.1016/j.ejmech.2016.06.002
Abstract

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 μM) against all Cancer cell lines, and could obviously induce Apoptosis of Cancer cell line U937 at 1.0 μM after 48 h treatment.

Keywords

2,5-Diketopiperazine derivatives; Apoptosis; Cytotoxic activity; Lipophilicity; Long alkyl chain.

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