Abstract Three 2-arylpiperidinyl-1,4-naphthoquinone derivatives were synthesized and evaluated in vitro to determine their cytotoxicity on cancer and normal cell lines. In order to establish their possible action mechanism, the electrochemical behaviour of these quinones was examined using cyclic voltammetry (CV) as technique by using a three-electrode setup: a glassy carbon, Ag/AgCl (in 3 M KCl), and platinum wire as working, reference, and counter electrodes, respectively. Kinetic studies were done to determine the control of the reduction reaction and the number of transferred electrons in the process. Furthermore, the addition of dsDNA to the quinone solutions allowed for the observation of an interaction between each quinone and dsDNA as the current-peaks became lower in presence of dsDNA. Otherwise, motivated to support the aforementioned results, electronic structure calculations at the TPSS-D3/6-31+G(d,p) level of theory were carried out in order to find the most favourable noncovalently bonded complexes between quinones and DNA. Noncovalent complexes formed between DNA and 2-arylpiperidinyl-1,4-naphthoquinones and stabilized by π-stacking interactions along with the well-known hydrogen-bonded complexes were found, with the former being more stable than the latter. These results suggest that the intercalation of these quinone derivatives in DNA is the most likely action mechanism.

中文翻译：

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揭示 DNA 与细胞毒性 2-Arylpiperidinyl-1,4-Naphthoquinone 衍生物之间的相互作用：一项联合电化学和计算研究

摘要 合成了三种 2-芳基哌啶基-1,4-萘醌衍生物，并在体外评估了它们对癌症和正常细胞系的细胞毒性。为了建立它们可能的作用机制，使用循环伏安法 (CV) 作为技术通过使用三电极设置来检查这些醌的电化学行为：玻璃碳、Ag/AgCl（在 3 M KCl 中）和铂丝分别作为工作电极、参比电极和对电极。进行动力学研究以确定还原反应的控制和过程中转移的电子数。此外，将 dsDNA 添加到醌溶液中可以观察到每个醌和 dsDNA 之间的相互作用，因为在 dsDNA 存在下电流峰值变低。除此以外，为了支持上述结果，进行了 TPSS-D3/6-31+G(d,p) 理论水平的电子结构计算，以找到醌和 DNA 之间最有利的非共价键复合物。发现在 DNA 和 2-芳基哌啶基-1,4-萘醌之间形成的非共价复合物与众所周知的氢键复合物一起通过 π 堆积相互作用稳定，前者比后者更稳定。这些结果表明这些醌衍生物在 DNA 中的嵌入是最可能的作用机制。发现了 4-萘醌并通过 π 堆积相互作用与众所周知的氢键配合物稳定，前者比后者更稳定。这些结果表明这些醌衍生物在 DNA 中的嵌入是最可能的作用机制。发现了 4-萘醌并通过 π 堆积相互作用与众所周知的氢键配合物稳定，前者比后者更稳定。这些结果表明这些醌衍生物在 DNA 中的嵌入是最可能的作用机制。