在这项工作中，成功地设计和合成了新型潜在蒽醌-替莫唑胺（TMZ）抗肿瘤杂化物N-(2-((9,10-二氧代-9,10-二氢蒽-1-基)氨基)乙基)-3-甲基-4-氧代-3,4-二氢咪唑[5,1-d][1,2,3,5]四氮唑-8-羧酰胺（C-1）和2-(9,10-二氧代-9,10-二氢蒽-1-基)氨基)乙基-3-甲基-4-氧代-3,4-二氢咪唑[5,1-d][1,2,3,5]四氮唑-8-羧酸酯（C-9）。C-1（C-9）的电化学行为涉及9,10-蒽醌环的可逆过程，TMZ环的不可逆还原和氧化过程。用ctDNA，聚（dG）和聚（dA）修饰玻璃碳电极（GCE）表面构建电化学生物传感器，评估C-1（C-9）与DNA相互作用引起的DNA氧化损伤。C-1（C-9）中的蒽环骨架和TMZ环可向DNA链表现出具有缩合和烷基化的双功能效应。DNA生物传感器在小鼠血清中具有良好的实用性。凝胶电泳的结果进一步证明C-1（C-9）能有效地插入到ctDNA中并破坏质粒的结构。最后，蒽醌-TMZ杂合物C-1对A549和GL261细胞具有很高的细胞毒性，可作为临床抗肿瘤治疗的新型和最佳候选药物。版权所有 © 2023 Elsevier B.V.。

In this work, novel potential anthraquinone-temozolomide (TMZ) antitumor hybrids N-(2-((9,10-dioxo-9,10-dihydroanthracen-1-yl)amino)ethyl)-3-methyl-4-oxo-3,4-dihydroimidazo [5, 1-d][1,2,3,5]tetrazine-8-carboxamide (C-1) and 2-(9,10-dioxo-9,10-dihydroanthracen-1-yl)amino) ethyl-3-methyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxylate (C-9) were designed and synthesized successfully. The electrochemical behaviors of C-1 (C-9) involved the reversible processes of 9,10-anthraquinone ring, the irreversible reduction and oxidation processes of TMZ ring. Electrochemical biosensors were constructed with ctDNA, poly (dG) and poly (dA) modifying the surface of glassy carbon electrode (GCE) to evaluate the DNA oxidative damage caused by the interaction of C-1 (C-9) with DNA. Anthracycline skeleton and TMZ ring in C-1 (C-9) could exhibit bifunctional effects with both intercalating and alkylation modes toward DNA strands. The DNA biosensor had good practicability in mouse serum. The results of gel electrophoresis further demonstrated that C-1 (C-9) could effectively intercalated into ctDNA and disrupt plasmid conformation. Finally, anthraquinone-TMZ hybrid C-1 possessed high cytotoxicity toward A549 and GL261 cells, which could be a novel and optimal candidate for the clinic antitumor treatment.Copyright © 2023 Elsevier B.V. All rights reserved.