Donepezil (DNP) is one of approved drugs to treat Alzheimer's disease (AD). However, the potential effect of DNP on DNA is still unclear. Therefore, the interaction of DNP with calf thymus DNA (DNA) was studied in vitro using spectroscopic and molecular docking methods. Steady‐state and transient fluorescence experiments showed that there was a clear binding interaction between DNP and DNA, resulting from DNP fluorescence being quenched using DNA. DNP and DNA have one binding site between them, and the binding constant (K_b) was 0.78 × 10⁴ L·mol⁻¹ at 298 K. In this binding process, hydrophobic force was the main interaction force, because enthalpy change (ΔH) and entropy change (ΔS) of DNP–DNA were 67.92 kJ·mol⁻¹ and 302.96 J·mol⁻¹·K⁻¹, respectively. DNP bound to DNA in a groove‐binding mode, which was verified using a competition displacement study and other typical spectroscopic methods. Fourier transform infrared (FTIR) spectrum results showed that DNP interacted with guanine (G) and cytosine (C) bases of DNA. The molecular docking results further supported the results of spectroscopic experiments, and suggested that both Pi‐Sigma force and Pi‐Alkyl force were the major hydrophobic force functioning between DNP and DNA.

中文翻译：

---

使用光谱和分子对接方法探索多奈哌齐与小牛胸腺DNA的结合模式

多奈哌齐（DNP）是已批准的治疗阿尔茨海默氏病（AD）的药物之一。但是，DNP对DNA的潜在作用仍不清楚。因此，在体外使用光谱和分子对接方法研究了DNP与小牛胸腺DNA（DNA）的相互作用。稳态和瞬态荧光实验表明，DNP和DNA之间存在明显的结合相互作用，这是由于DNP荧光被DNA猝灭了。DNP与DNA之间有一个结合位点，在298 K时的结合常数（K _b）为0.78×10 ⁴ L·mol ^-1。在该结合过程中，由于焓变（ΔH），疏水力是主要的相互作用力。 ）和DNP–DNA的熵变（ΔS）为67.92 kJ·mol ^-1和302.96 J·mol ^-1 ·K ^-1。DNP以凹槽结合模式与DNA结合，这已通过竞争置换研究和其他典型的光谱学方法得到验证。傅里叶变换红外（FTIR）光谱结果表明DNP与DNA的鸟嘌呤（G）和胞嘧啶（C）碱基相互作用。分子对接的结果进一步支持了光谱实验的结果，并表明Pi-Sigma力和Pi-烷基力都是DNP和DNA之间的主要疏水力。