抗癌药物阿比特龙与脱氧核糖核酸的相互作用

V. Pronina, L. Agafonova, R. Masamrekh, A. Kuzikov, V. Shumyantseva
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引用次数: 2

摘要

采用差分脉冲伏安法研究了双链DNA (dsDNA)及其与抗肿瘤药物醋酸阿比特龙(AA)络合物的电分析特性。利用功能化碳纳米管修饰的丝网印刷电极,通过改变嘌呤杂环碱基鸟嘌呤和腺嘌呤的电化学氧化强度,证明了醋酸阿比特龙对dsDNA的影响。[dsDNA-AA]复合物对鸟嘌呤和腺嘌呤的结合常数(Kb)分别为1.63×104 M-1和1.93×104 M-1。在醋酸阿比特龙存在的情况下,鸟嘌呤和腺嘌呤的电化学氧化信号强度与不含药物的核碱基的电化学氧化信号强度之比(%)计算出毒性效应的电化学系数。当乙酸阿比特龙的浓度超过60 μM时,鸟嘌呤和腺嘌呤的电化学氧化电流下降了50%或更多。通过对电化学参数和结合常数的分析,提出了醋酸阿比特龙与DNA相互作用的机理,主要是通过小凹槽形成氢键。电化学DNA生物传感器首次用于研究抗癌药物醋酸阿比特龙与dsDNA的相互作用机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interaction of the Anticancer Drug Abiraterone with dsDNA
The electroanalytical characteristics of double-stranded DNA (dsDNA) and the complex of dsDNA and the antitumor drug abiraterone acetate (AA) were studied by differential pulse voltammetry. The effect of abiraterone acetate on dsDNA was shown, which was registered by alteration the intensity of electrochemical oxidation of purine heterocyclic bases guanine and adenine using screen printed electrodes modified with functionalized carbon nanotubes. The binding constants (Kb) of the [dsDNA-AA] complex for guanine and adenine were 1.63×104 M-1 and 1.93×104 M-1, respectively. The electrochemical coefficients of the toxic effect were calculated as the ratio of the intensity of the electrochemical oxidation signals of guanine and adenine, in the presence of abiraterone acetate to the intensity of the electrooxidation signals of these nucleobases  without drug (%). At concentrations of abiraterone acetate exceeding 60 μM, a decrease in the currents of electrochemical oxidation of guanine and adenine by 50% or more is recorded. Based on the analysis of electrochemical parameters and values ​​of binding constants, an assumption was made about the mechanism of interaction of abiraterone acetate with DNA, mainly due to the formation of hydrogen bonds with the minor groove. An electrochemical DNA biosensor was first used to study the mechanism of interaction of the anticancer drug abiraterone acetate with dsDNA.
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