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-MC...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2023-05, Vol.415 (12), p.2249-2260
Main Authors: Guo, Fei-Fei, Li, Tong, Mu, Xi-Ping, Zhang, Xue, Xu, Zhi-Hao, Sun, Ping, Yu, Ri-Lei, Xia, Ya-Mu, Gao, Wei-Wei
Format: Article
Language:English
Subjects:
Adenine
Analysis
Analytical Chemistry
Anticancer properties
Antimitotic agents
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biochemistry
Calf thymus
Cell proliferation
Characterization and Evaluation of Materials
Chemical synthesis
Chemistry
Chemistry and Materials Science
Damage
Deoxyribonucleic acid
DNA
DNA - genetics
DNA Damage
Electrochemical analysis
Electrochemistry
Electrophoresis
Fluorescence
Food Science
Gel electrophoresis
Laboratory Medicine
Mitoxantrone
Monitoring/Environmental Analysis
Oxidation
Oxidative Stress
Properties
Pteridine
Pteridines
Research Paper
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Summary: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
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-023-04643-5