Analytical and Bioanalytical Chemistry ( IF 3.8 ) Pub Date : 2023-03-15 , DOI: 10.1007/s00216-023-04643-5 Fei-Fei Guo 1 , Tong Li 1 , Xi-Ping Mu 1 , Xue Zhang 1 , Zhi-Hao Xu 1 , Ping Sun 1 , Ri-Lei Yu 2 , Ya-Mu Xia 1 , Wei-Wei Gao 1
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In this work, we design and synthesize 2,2′-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1,3(2H,4H)-diyl)bis(N,N-bis(2-chloroethyl)acetamide) (PT-MCA) as a novel DNA intercalator and potential antitumor agent. Electrochemical analysis reveals the redox process of PT-MCA on the electrode surface. The bioelectrochemical sensors are obtained by modifying the surface of GCE with calf thymus DNA (ctDNA), poly (dG), poly (dA), and G-quadruplex, respectively. The DNA oxidative damage induced by PT-MCA is investigated by comparing the peak intensity change of dGuo and dAdo and monitoring the peaks of the oxidation products of guanine and/or adenine (8-oxoGua and/or 2,8-oxoAde). UV–vis absorption and fluorescence spectra and gel electrophoresis are further employed to understand the intercalation of PT-MCA into DNA base pairs. Moreover, PT-MCA is proved to exhibit stronger anti-proliferation activity than mitoxantrone against both 4T1 and B16-F10 cancer cells. At last, the oxidative damage of PT-MCA toward ctDNA is not interfered by the coexistence of ions and also can be detected in real serums.
Graphical abstract
中文翻译：
潜在嘧啶并 [5,4-g] 蝶啶衍生抗肿瘤剂对 DNA 氧化损伤的电化学检测
在这项工作中，我们设计并合成了 2,2'-(7,9-dimethyl-2,4,6,8-tetraoxo-6,7,8,9-tetrahydropyrimido[5,4-g]pteridine-1, 3(2H,4H)-二基)双( N,N-双（2-氯乙基）乙酰胺）（PT-MCA）作为一种新型 DNA 嵌入剂和潜在的抗肿瘤剂。电化学分析揭示了 PT-MCA 在电极表面的氧化还原过程。生物电化学传感器是通过分别用小牛胸腺 DNA (ctDNA)、聚 (dG)、聚 (dA) 和 G-四链体修饰 GCE 的表面获得的。通过比较 dGuo 和 dAdo 的峰强度变化并监测鸟嘌呤和/或腺嘌呤（8-oxoGua 和/或 2,8-oxoAde）氧化产物的峰，研究了 PT-MCA 诱导的 DNA 氧化损伤。进一步采用紫外-可见吸收和荧光光谱以及凝胶电泳来了解 PT-MCA 嵌入 DNA 碱基对中。此外，PT-MCA 被证明对 4T1 和 B16-F10 癌细胞表现出比米托蒽醌更强的抗增殖活性。
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