Electrochemical detection of the oxidative damage of a potential pyrimido[5,4-g]pteridine-derived antitumor agent toward DNA
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.
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Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:415 |
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| Enthalten in: |
Analytical & bioanalytical chemistry - 415(2023), 12 vom: 15. März, Seite 2249-2260 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Fei-Fei [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Antitumor agent |
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| Anmerkungen: |
© Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s00216-023-04643-5 |
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| funding: |
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| 520 | |a 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 | ||
| 650 | 4 | |a DNA intercalator | |
| 650 | 4 | |a Electrochemical DNA biosensor | |
| 650 | 4 | |a Oxidative damage | |
| 650 | 4 | |a Antitumor agent | |
| 700 | 1 | |a Li, Tong |4 aut | |
| 700 | 1 | |a Mu, Xi-Ping |4 aut | |
| 700 | 1 | |a Zhang, Xue |4 aut | |
| 700 | 1 | |a Xu, Zhi-Hao |4 aut | |
| 700 | 1 | |a Sun, Ping |4 aut | |
| 700 | 1 | |a Yu, Ri-Lei |4 aut | |
| 700 | 1 | |a Xia, Ya-Mu |4 aut | |
| 700 | 1 | |a Gao, Wei-Wei |0 (orcid)0000-0003-0676-790X |4 aut | |
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