中文摘要：

以O2-2,4-二硝基苯基偶氮鎓二醇盐（PABA/NO）为先导化合物,选择适当的仲胺作为偶氮鎓二醇盐中相应的胺片段,并用碳氮键取代苯环5位的碳氧酯键,设计合成了化合物2a,2b和4a4j,以期获得活性更强且稳定性好的抗肿瘤药物.目标化合物经1H NMR,13C NMR及HRMS进行了结构确证.生物活性测试结果表明,目标化合物可不同程度地抑制结肠癌HCT-116细胞的增殖,其中化合物4h的活性最强（IC50=7.945±0.421μmol/L）,优于PABA/NO（IC50=12.134±0.675μmol/L）.NO释放实验结果表明,此类化合物的NO释放量与细胞毒性呈正相关.化合物4h在HCT-116细胞中释放NO的量最多,约是正常细胞的2倍.此外,化合物4h在大鼠血浆中的体外稳定性显著优于PABA/NO,值得进一步研究.

英文摘要：

O2-（ 2,4-Dinitrophenyl） diazeniumdiolate（ PABA/NO） possesses significant anticancer activity but poor stability. To search for new agents with stronger activity and better stability,PABA/NO was employed as a lead compound. A series of PABA/NO analogues was designed and synthesized with an appropriate secondary amine as the amine moiety in the diazeniumdiolate structure,and replacing the ester bond of the benzene ring with a carbon-nitrogen bond. The structures of the synthesized compounds were characterized by means of 1H NMR,13C NMR and HRMS. All the target compounds showed strong inhibitory effects against colon cancer HCT-116 cells to a varying extent. Compound 4h（ IC50= 7. 945 ± 0. 421 μmol/L） was the most potent against HCT-116 cells,superior to PABA/NO（ IC50= 12. 134 ± 0. 675 μmol/L）. There was observed that a positive correlation existed between activity and NO release levels. The most active compound 4h released higher levels of NO in colon cancer cells than that in the normal ones. In addition,compound 4h showed better stability in plasma than PABA/NO. These results suggested compound 4h might be a promising anticancer agent,and worthy of further study.