Abstract
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.
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Funding
This work is partially supported by the National Natural Science Foundation of China (No. 21472105), the Natural Science Foundation of Shandong Province (No. ZR2020QB168), the Key Laboratory of Processing and Quality Evaluation Technology of Green Plastics of China National Light Industry Council (Grant PQETGP2022002), the Beijing Science and Technology Plan Project (Grant Z211100004321003, Z211100004321004), and the Scientific Research Foundation of Qingdao University of Science and Technology (No. 010029049).
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Guo, FF., Li, T., Mu, XP. et al. Electrochemical detection of the oxidative damage of a potential pyrimido[5,4-g]pteridine-derived antitumor agent toward DNA. Anal Bioanal Chem 415, 2249–2260 (2023). https://doi.org/10.1007/s00216-023-04643-5
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DOI: https://doi.org/10.1007/s00216-023-04643-5