Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives
Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives
复制标题
DOI：
10.1016/j.ejmech.2016.06.002
复制
发表时间：
2016-10-04
影响因子：
6.7
通讯作者：
Liu, Yonghong
中科院分区：
文献类型：
--
作者：
Liao, Sheng-Rong;Qin, Xiao-Chu;Liu, Yonghong
设计、合成了一系列新型n -1-单烯丙化2,5-二酮哌嗪衍生物，并通过CCK8测定对8种癌细胞进行了细胞毒性评价。这些衍生物在2,5-二酮哌嗪环的C-6位置被甲氧基苯基取代，在c -3位置被各种长烷基侧链取代。细胞毒性结果表明，4-甲氧基苯基优于2-甲氧基苯基，而3-甲氧基苯基不适合作为替代基团。当长烷基侧链上亚甲基的数目（n值）为3时（化合物1c和3c），衍生物具有最强的细胞毒性。4-甲氧基苯基和戊基侧链取代的化合物3c对所有癌细胞均有较强的抑制活性（IC50 = 0.36 ~ 1.9 μ M），在处理48h后1.0 μ M可明显诱导癌细胞U937凋亡。(C) 2016 Elsevier Masson SAS。版权所有。
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.