双取代蒽醌-多胺缀合物的合成及其抗肿瘤细胞增殖活性研究

Synthesis and antitumor activity of bis-substituted anthraquinone-polyamine conjugates

目的设计合成系列蒽醌-多胺缀合物，并对其体外抗肿瘤活性及其与DNA的结合能力进行初步评价。方法以1，4-二羟基蒽醌、1，8-二氯蒽醌等为起始原料，通过多步反应合成目标化合物；以米托蒽醌为阳性对照，采用MTT法测试目标化合物对K562、HepG2、HT-29、HCT-116四种肿瘤细胞的体外细胞毒性；并对部分化合物进行了与DNA的结合实验。结果与结论合成了7个未见文献报道的新化合物，其结构经^1H-NMR、APCI-MS和元素分析确认。体外活性实验结果显示，多数化合物对肿瘤细胞具有一定的抑制作用，化合物T2-T4尤其是化合物T3对HepG2细胞和HCT-116细胞的生长抑制作用强于阳性对照物米托蒽醌。DNA结合实验表明化合物T3以嵌入方式作用于DNA，使鲱鱼精DNA—EB体系的荧光产生淬灭现象。

Series of anthraquinone-polyamine derivatives were designed and synthesized. As the raw materials, 1,8-dichloroanthracene-9, 10-dione or 1,4-dihydroxyanthracene-9, 10-dione were used to obtain the compounds by multi-steps reactions including substitution, sulfonation, substitution, acidizing reaction. The structures of the synthesized compounds were confirmed by ^1H-NMR, MS and elemental analysis. The in vitro antitumor activities of these compounds were evaluated on K562, HepG2, HT-29 and HCT-116 tumor cells by MTT assay, with mitoxantrone as the reference compound. The results indicated that the most of target compounds exhibited potent cell-growth inhibition effects on the tested cell lines. Among them, compounds T2 - T4 showed better activities against HepG2 and HCT-116 cells than mitoxantrone. Compound T3 can intercalate into DNA, with intensively fluorescence quenching in herring sperm DNA-EB system.