In this work, we designed and synthesized two novel 2-nitroimidazole-naphthalimide-derived antitumor agents N-(2-(naphthalimide)ethyl)-2-(2-nitroimidazole)acetamide (D-2) and N-(2-(5-nitro-naphthalimide)ethyl)-2-(2-nitroimidazole)acetamide (D-5). The oxidative damage induced by the interaction between D-2 (D-5) and DNA was investigated by CV and DPV. The efficient electrochemical biosensors were prepared through modifying GCE with calf thymus DNA, poly dA and poly dG, respectively. The redox mechanism of D-2 (D-5) on GCE surface involved the reduction of 2-nitro group on imidazole ring and the oxidation of methylene linked naphthalimide skeleton and 2-nitroimidazole. The results of voltametric evaluation of interaction between antitumor agent and DNA/GCE revealed the oxidative damage of DNA caused by D-2 (D-5). In addition, UV–vis absorption and fluorescence spectra were investigated to further distinguish the interaction mode between D-2 (D-5) and DNA, implying the intercalation mode of D-2 (D-5) toward base pairs of DNA with a high affinity. At last, D-2 and D-5 were proved to have significantly better cell selectivity than mitonafide, the fact indicated that D-2 and D-5 had the potential for becoming lead antitumor agents and eliminating the side effects toward normal cells.

在这项工作中，我们设计并合成了两种新型2-硝基咪唑-萘酰亚胺衍生的抗肿瘤剂N- (2-(萘酰亚胺)乙基)-2-(2-硝基咪唑)乙酰胺( D-2 )和N- (2-( 5-硝基萘酰亚胺）乙基）-2-（2-硝基咪唑）乙酰胺（D-5）。通过CV和DPV研究了D-2（D-5）与DNA相互作用引起的氧化损伤。分别用小牛胸腺DNA、poly dA和poly dG修饰GCE，制备出高效的电化学生物传感器。D-2（D-5）的氧化还原机制) 在 GCE 表面上涉及咪唑环上 2-硝基的还原和亚甲基连接的萘酰亚胺骨架和 2-硝基咪唑的氧化。抗肿瘤剂与DNA/GCE相互作用的伏安评估结果揭示了D-2（D-5）对DNA的氧化损伤。此外，还研究了紫外-可见吸收和荧光光谱，以进一步区分D-2 ( D-5 ) 和 DNA 之间的相互作用模式，暗示D-2 ( D-5 ) 对 DNA 碱基对的嵌入模式亲和力高。最后，D-2和D-5被证明比米托那芬具有明显更好的细胞选择性，事实表明D-2和D-5有可能成为主要的抗肿瘤药物并消除对正常细胞的副作用。