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

Shengrong Liao, Xiaochu Qin, Ding Li, Zhengchao Tu, Jinsheng Li, Xuefeng Zhou, Junfeng Wang, Bin Yang, Xiuping Lin, Juan Liu, Xianwen Yang, Yonghong Liu

Index: Eur. J. Med. Chem. 83 , 236-44, (2014)

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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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.