含氟2,5-二酮哌嗪衍生物的设计、合成及细胞毒活性

Design, synthesis and cytotoxic activities of fluorine-containing 2, 5-diketopiperazine derivatives

摘要: 以N，N-二乙酰基-2，5-二酮哌嗪、烯丙基溴、邻氟苯甲醛和其他芳香醛为原料，合成得到21 个新型的含氟2，5-二酮哌嗪衍生物( 2a ~ 2u )，其结构经¹H NMR、¹³C NMR和HRMS确证。采用CCK8法初步测试了目标化合物对10株肿瘤细胞(K562，U937，MOLT-4，HL60，HeLa，DU145，MCF-7，A549，SGC-7901和H1975)的体外抑制活性。结果表明:目标化合物 2a ， 2d ， 2e ， 2f ， 2g ， 2h ， 2k 和 2t 均显示了良好的广谱的细胞毒活性，其中化合物 2t 对U937、HeLa和DU145细胞的半数抑制浓度(IC₅₀)分别为0.2、0.5和0.7 μmol/L，其作为潜在的抗肿瘤活性先导化合物值得进一步深入研究。

Abstract: Twenty-one novel fluorine-containing 2, 5-diketopiperazine derivatives( 2a - 2u )were synthesized by using N, N-diacetyl-2, 5-diketopiperazine, allylbromide, 2-fluorobenzaldehyde and other aromatic aldehydes. The structures were characterized by ¹H NMR, ¹³C NMR, and HRMS. The cytotoxicities were evaluated against ten human tumour cell lines(K562, U937, MOLT-4, HL60, HeLa, DU145, MCF-7, A549, SGC-7901, H1975)by using CCK8 assay. Results showed that compounds 2a , 2d , 2e , 2f , 2g , 2h , 2k , and 2t showed significant cytotoxicity against U937(IC₅₀=0. 2 μmol/L), HeLa(IC₅₀=0. 5 μmol/L), and DU145(IC₅₀=0. 7 μmol/L), respectively. Compound 2t could become a lead compound for further development for anticancer agents.