Lafam-Laboratory for Pharmaceutical and Environmental Analysis, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia 74605-170, Brazil.
LabMol-Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia 74605-170, Brazil.
Molecules. 2021 Dec 16;26(24):7623. doi: 10.3390/molecules26247623.
The binding between anticancer drugs and double-stranded DNA (dsDNA) is a key issue to understand their mechanism of action, and many chemical methods have been explored on this task. Molecular docking techniques successfully predict the affinity of small molecules into the DNA binding sites. In turn, various DNA-targeted drugs are electroactive; in this regard, their electrochemical behavior may change according to the nature and strength of interaction with DNA. A carbon paste electrode (CPE) modified with calf thymus ds-DNA (CPDE) and computational methods were used to evaluate the drug-DNA intercalation of doxorubicin (DOX), daunorubicin (DAU), idarubicin (IDA), dacarbazine (DAR), mitoxantrone (MIT), and methotrexate (MTX), aiming to evaluate eventual correlations. CPE and CPDE were immersed in pH 7 0.1 mM solutions of each drug with different incubation times. As expected, the CPDE response for all DNA-targeted drugs was higher than that of CPE, evidencing the drug-DNA interaction. A peak current increase of up to 10-fold was observed; the lowest increase was seen for MTX, and the highest increase for MIT. Although this increase in the sensitivity is certainly tied to preconcentration effects of DNA, the data did not agree entirely with docking studies, evidencing the participation of other factors, such as viscosity, interfacial electrostatic interactions, and coefficient of diffusion.
抗癌药物与双链 DNA（dsDNA）的结合是理解其作用机制的关键问题，为此已经探索了许多化学方法。分子对接技术成功地预测了小分子与 DNA 结合位点的亲和力。反过来，许多针对 DNA 的药物具有电化学活性；在这方面，它们的电化学行为可能会根据与 DNA 的相互作用的性质和强度而发生变化。使用小牛胸腺 ds-DNA（CPDE）修饰的碳糊电极（CPE）和计算方法来评估阿霉素（DOX）、柔红霉素（DAU）、伊达比星（IDA）、达卡巴嗪（DAR）、米托蒽醌（MIT）和甲氨蝶呤（MTX）的药物-DNA 插入，旨在评估可能的相关性。将 CPE 和 CPDE 浸入每种药物在不同孵育时间的 pH 7 0.1 mM 溶液中。正如预期的那样，所有针对 DNA 的药物对 CPDE 的响应都高于 CPE，这表明存在药物-DNA 相互作用。观察到电流峰值增加了 10 倍；MTX 的增加最小，MIT 的增加最大。尽管这种灵敏度的提高肯定与 DNA 的预浓缩效应有关，但数据与对接研究并不完全一致，表明存在其他因素的参与，例如粘度、界面静电相互作用和扩散系数。
