一种新型三唑嘧啶酮衍生物:研究 DNA 相互作用的便携式电化学方法

Arif Engin Çeti̇n
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摘要

本研究合成了一种新型三唑嘧啶酮衍生物--2-(2-氯苯基)-5-(吗啉甲基)-[1,2,4]三唑并[1,5-a]嘧啶-7(3H)-酮,简称 CPD-1,作为候选药物。我们采用电化学技术分析了该化合物的电化学行为及其与单链 DNA(ssDNA)和双链 DNA(dsDNA)的相互作用。我们使用差分脉冲伏安法(DPV)和循环伏安法(CV)研究了 pH 值、浓度、扫描速率、固定时间等实验参数,以获得最精确的分析信号。我们提出了一种创新方法来评估这种候选药物对 DNA 的毒性影响。我们还提出了一个简化方程,根据药物与 DNA 相互作用前后电化学信号(特别是鸟嘌呤碱基的峰值电流)的变化来量化毒性效应。我们的方法为新兴的电化学毒性评估领域做出了贡献,并有望推动药物开发和安全性评估。此外,我们还在不同的日期对候选药物进行了稳定性测试。值得注意的是,我们的研究发现,CPD-1 与 ssDNA 和 dsDNA 相互作用时,鸟嘌呤碱基会发生显著变化,这突出表明了这些化合物对 DNA 结构的潜在影响。根据我们的实验数据,我们得出结论:由于 CPD-1 对 DNA 有影响,因此可以将其用作药物。
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A Novel Triazolopyrimidinone Derivative: A Portable Electrochemical Approach to Investigate DNA Interactions
In this study, a novel triazolopyrimidinone derivative, 2-(2-chlorophenyl)-5-(morpholinomethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one, abbreviated as CPD-1, was synthesized as a drug candidate. By employing electrochemical techniques, we analyzed the electrochemical behavior of this compound and its interactions with both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Experimental parameters such as pH, concentration, scan rate, immobilization time were studied using Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV) to obtain the most precise analytical signals. We present an innovative approach to evaluate the toxicity effect of this drug candidate on DNA. We also propose a simplified equation to quantify toxicity effects based on changes in electrochemical signals, specifically peak current of guanine bases, before and after drug-DNA interactions. Our methodology contributes to the burgeoning field of electrochemical toxicity assessment and holds promise for advancing drug development and safety evaluation. Furthermore, stability tests for the drug candidate were conducted on different days. Notably, our investigation revealed significant alterations in guanine bases upon the interaction of CPD-1 with both ssDNA and dsDNA, underscoring the potential impact of these compounds on DNA structure. Based on our experimental data, we conclude that this molecule can be utilized as a drug due to its effects on DNA.
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