替硝唑与金属离子对盐酸利多卡因-血清白蛋白相互作用的荧光和紫外-可见光谱和热量及分子模拟

doi:10.19286/j.cnki.cci.2026.06.029

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摘要

从分子水平上理解联合使用的双药物与生物大分子的相互作用机制，有助于开发有效的治疗方法。旨在探究替硝唑（TNZ）与金属离子对盐酸利多卡因（LDC）和牛血清白蛋白（BSA）相互作用的影响，重点阐明其结合模式、结构特征及热力学性质。光谱实验研究表明，荧光猝灭速率常数（Kq）值都小于最大动态猝灭速率常数，且Kq和结合常数（Kb）都随温度升高而增大，紫外吸收光谱也未发生变化。实验证明，在替硝唑的影响下，盐酸利多卡因以动态猝灭的模式抑制蛋白的荧光强度。负的摩尔吉布斯能（ΔG>0）表明相互作用过程是自发的。正的焓变（ΔH>0）和负的熵变（ΔS<0）表明缔合过程中疏水作用力主要参与其中。替硝唑和盐酸利多卡因插入到血清白蛋白亚结构域IA（位点III）的疏水腔中，形成了一个结合位点。通过希尔方程的结果表明替硝唑与盐酸利多卡因表现出正协同作用的特征。同步荧光的结果表明，与替硝唑和盐酸利多卡因作用后，BSA的结构发生了变化。双药物和牛血清白蛋白的结合明显降低了牛血清白蛋白中酪氨酸（Tyr）残基和色氨酸（Trp）残基周围微环境的疏水性。分子对接（MD）研究进一步支持了荧光光谱实验结果。此外，所考察的金属离子（Fe3+、Cu2+、Mg2+等）均能显著增强药物与BSA的亲和力和两种药物之间的正协同效应。由此获得的结果有助于深入了解药物-蛋白质相互作用模式，从而为生物医学和药物学研究者在药物的合理设计以及开发更有效和更有针对性的治疗方法方面提供帮助和指导。

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	刘里
	张梦秋

关键词 ：替硝唑, 盐酸利多卡因, 金属离子, 分子模拟, 联合用药, 荧光和紫外-可见光谱法

Abstract：

Understanding the interaction mechanism of dual drugs towards bio-macromolecules at molecular level can help in developing effective therapeutics. The influence of tinidazole (TNZ) and metal ions on the binding of lidocaine hydrochloride (LDC) to bovine serum albumin (BSA), with a focus on binding mode, structural characteristics, and thermodynamic properties were investigated. Spectroscopic experimental studies have shown that the fluorescence quenching rate constant (Kq) is always smaller than the maximum dynamic quenching rate constant, and both Kq and the binding constant (Kb) increase with increasing temperature. The ultraviolet absorption spectrum remains unchanged. These experimental results demonstrate that under the influence of tinidazole, lidocaine hydrochloride inhibits the fluorescence intensity of protein in a dynamic quenching mode. The negative molar Gibbs energy suggested the spontaneity of the interaction process. The positive enthalpy and negative entropy changes indicated the involvement of hydrophobic forces during the association process. In the binding process, tinidazole and idocaine hydrochloride was inserted into the hydrophobic cavity of subdomain IA (site III) of serum albumin, forming a binding site. Through the calculation of Hill's equation, it was found that tinidazole and lidocaine hydrochloride exhibited positive cooperative effects. Synchronous fluorescence result indicates structural change of BSA upon association with tinidazole and lidocaine hydrochloride. The bingding of dual drugs and BSA led to a significantly reduction in the hydrophobicity of the microenvironment around tyrosine (Tyr) and tryptophan (Trp) residues in BSA. Molecular docking (MD) study further supports the results of the fluorescence spectroscopy experiments. Moreover, the investigated metal ions (Fe3+, Cu2+, Mg2+, etc.) could significantly enhance the affinity of the drugs to BSA and the positive cooperative effect between the two drugs. The results obtained thus advance our insights into drug-protein interaction patterns which provide help and guidance to biomedical and pharmaceutical researchers for the rational designing of drugs and for the development of more effective and targeted therapies.

Key words： tinidazole lidocaine hydrochloride metal ions molecular simulation combination drug fluorescence and UV-Vis spectroscopy

基金资助:

国家自然科学基金青年科学基金项目（No. 21804079）；曲靖市科学技术局·曲靖师范学院科技创新联合专项（No. KJLH2024YB04）；
曲靖师范学院天然药用功能分子发现及生物转化创新团队、曲靖师范学院博士创新团队、云南省科技厅科技人才与平台
计划项目（Nos. 202305AF150088、202405AF140016）项目资助

作者简介: 刘里（ 1982— ），女，吉林吉林人，副教授。

引用本文:

刘里，张梦秋. 替硝唑与金属离子对盐酸利多卡因-血清白蛋白相互作用的荧光和紫外-可见光谱和热量及分子模拟[J]. 煤炭与化工, 2026, 49(6): 145-155. Liu Li, Zhang Mengqiu. Fluorescence and UV-Vis spectroscopic, calorimetric and molecular modeling studies on the interactions between lidocaine hydrochloride and serum albumin influenced by tinidazole and metal ions. CCI, 2026, 49(6): 145-155.

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http://www.mtyhg.com.cn/CN/10.19286/j.cnki.cci.2026.06.029 或 http://www.mtyhg.com.cn/CN/Y2026/V49/I6/145

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