摘要
In this work, an efficient electrochemical biosensor for the detection of DNA damage induced by the interaction of a novel antitumor agent AD-NU was investigated by CV , DPV and SWV methods. The GCE was modified with calf thymus DNA, G-quadruplexes, poly dA and poly dG, respectively. Among all the candidates, compound AD-NU was the optimum ligand because of the minimum energy when binding to DNA or TOP II by molecular docking. The electrochemical analysis revealed the redox mechanism of AD-NU on the GCE surface, which included two consecutive reversible processes of 9,10-diquinone and irreversible redox of nitroso group . The DNA damage caused by AD-NU was investigated by comparing the intensity changes of dGuo and dAdo oxidation peaks in DNA strands, and monitoring the appearance of peak for oxidative product 8-oxoGua. Further confirmation for the interaction between AD-NU and DNA was performed by UV–vis absorption and fluorescence titration, which implied the intercalation of AD-NU into DNA base pairs with a high affinity constant ( K b = 13.7 ×10 5 M −1 ). The electrophoresis also revealed the potency of AD-NU to cleave and unwind DNA strands. Finally, AD-NU was proved to have good antiproliferative activity toward tumor cells, with IC 50 values of 3.0 μmol ∙ L −1 for A549 cell lines and 3.3 μmol ∙ L −1 for Hela cell lines, superior to MTZ reference.
危险品化学品经营许可证（带存储）