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

作者:Sheng-Rong Liao, Xiao-Chu Qin, Zhen Wang , Ding Li, Liang Xu, Jin-Sheng Li, Zheng-Chao Tu, Yonghong Liu*

刊物:European Journal of Medicinal Chemistry

刊号:2016,121:500-509

摘要: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?0.36e1.9 mM) against all cancer cell lines, and could obviously induce apoptosis of cancer cell line U937 at 1.0 mM after 48 h treatment.