title: Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents.
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.
authors: 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.
authors: Shengrong
authors: S
authors: Liao
authors: Laboratory of Molecular Engineering and Laboratory of Natural Product Synthesis, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
authors: Xiaochu
authors: X
authors: Qin
authors: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
authors: Ding
authors: D
authors: Li
authors: Laboratory of Molecular Engineering and Laboratory of Natural Product Synthesis, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
authors: Zhengchao
authors: Z
authors: Tu
authors: 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.
authors: Jinsheng
authors: J
authors: Li
authors: 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.
authors: Xuefeng
authors: X
authors: Zhou
authors: 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.
authors: Junfeng
authors: J
authors: Wang
authors: 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.
authors: Bin
authors: B
authors: Yang
authors: 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.
authors: Xiuping
authors: X
authors: Lin
authors: 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.
authors: Juan
authors: J
authors: Liu
authors: 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.
authors: Xianwen
authors: X
authors: Yang
authors: 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: yonghongliu@scsio.ac.cn.
authors: Yonghong
authors: Y
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D054659:Diketopiperazines
keywords: 2,5-Diketopiperazine derivative; Anticancer agent; Protective group; Solubility