Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents

  • Eur J Med Chem. 2014 Aug 18:83:236-44. doi: 10.1016/j.ejmech.2014.06.030.
Shengrong Liao  1 ,  Xiaochu Qin  2 ,  Ding Li  3 ,  Zhengchao Tu  2 ,  Jinsheng Li  1 ,  Xuefeng Zhou  1 ,  Junfeng Wang  1 ,  Bin Yang  1 ,  Xiuping Lin  1 ,  Juan Liu  1 ,  Xianwen Yang  1 ,  Yonghong Liu  4
Affiliations
  • 1. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
  • 2. Laboratory of Molecular Engineering and Laboratory of Natural Product Synthesis, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
  • 3. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
  • 4. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China. Electronic address: [email protected].
PMID: 24960627 DOI: 10.1016/j.ejmech.2014.06.030
Abstract

Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their Anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum Anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC50 = 0.5-4.5 μM), especially to the Cancer cell lines U937 (IC50 = 0.5 μM) and K562 (IC50 = 0.9 μM). Compound 4m could become a lead compound for further development for Anticancer agents.

Keywords
2,5-Diketopiperazine derivative; Anticancer agent; Protective group; Solubility.