光谱法和分子对接模拟研究去甲去氢斑蝥酰亚胺缩肉桂醛与人血清白蛋白的相互作用

doi:10.3964/j.issn.1000-0593(2025)10-2783-07

摘要
参考文献
相关文章 (15)

全文: PDF (8944 KB)
输出: BibTeX | EndNote (RIS)

摘要：去甲去氢斑蝥素类化合物是一类具有抗癌活性的药物，其与人血清白蛋白（HSA）的相互作用机理对了解该类药物的性质具有重要意义。以呋喃、肉桂醛和马来酸酐为原料，合成了去甲去氢斑蝥酰亚胺缩肉桂醛（DCIC），其结构经NMR确证。采用荧光光谱法、位点竞争和分子对接模拟研究了DCIC与HSA的相互作用机理。荧光光谱表明，DCIC对HSA的猝灭机制为静态猝灭，在298、303和313 K时，猝灭常数分别是8.53×10⁴、7.05×10⁴和6.05×10⁴ L·mol^-1；303 K时结合位点数为0.978，吉布斯自由能为-25.75 kJ·mol^-1；焓变ΔH＜0，熵变ΔS＜0，可知DCIC与HSA之间的作用力主要是氢键和范德华力。根据Forster能量转移定律，计算出两者间结合距离为3.946 nm，小于7 nm，表明DCIC对HSA为非辐射能量转移的静态猝灭。同步荧光显示该化合物使色氨酸（Trp）残基周围微环境的疏水性增加。位点竞争实验表明DCIC与HSA主要是在亚结构域ⅡA (site Ⅰ）结合。分子对接模拟表明DCIC与HSA主要通过氢键结合，最优结合能为-25.44 kJ·mol^-1，结合位点为site Ⅰ，结果与光谱法、位点竞争实验一致。本研究结果可以为DCIC在人体的贮存、运输、药代动力学等研究提供重要的理论依据。

关键词：去甲去氢斑蝥素；肉桂醛；人血清白蛋白；光谱法；分子对接模拟

Abstract：Dehydronorcantharidin compounds are a class of drugs with anticancer activity. The interaction mechanism between compounds and human serum albumin (HSA) is of great significance for understanding the properties of such drugs. In this study, dehydronorcantharidin imide-cinnamaldehyde (DCIC) was synthesized from furan, cinnamaldehyde and maleic anhydride, and the structure of the target compound was confirmed by NMR spectroscopy. The interaction mechanism of DCIC with HSA was investigated using fluorescence spectroscopy, site marker competition and molecular docking simulations. Fluorescence spectroscopy results indicated that the quenching mechanism of DCIC towards HSA followed a static quenching model. The quenching constants at 298, 303, and 313 K were found to be 8.53×10⁴, 7.05×10⁴, and 6.05×10⁴ L·mol^-1, respectively. At 303 K, the number of binding sites was calculated to be 0.978, and the Gibbs free energy is -25.75 kJ·mol^-1. Both the enthalpy change (ΔH) and entropy change (ΔS) were negative, suggesting that the main interaction forces between DCIC and HSA were hydrogen bonds and van der Waals forces. According to Förster's theory of energy transfer, the binding distance between DCIC and HSA was calculated to be 3.946 nm, which is less than 7 nm, indicating static quenching through non-radiative energy transfer. Synchronous fluorescence spectroscopy results further revealed that DCIC increased the hydrophobicity of the microenvironment surrounding the tryptophan residue. Molecular docking simulations showed that DCIC binds to HSA at site I through a hydrogen bond, with an optimal binding energy of -25.44 kJ·mol^-1, which is consistent with the findings from the spectroscopic and site competition experiments. This study provides a crucial theoretical foundation for research on the storage, transport, and pharmacokinetics of DCIC within the human body.

Key words：Dehydronorcantharidin; Cinnamaldehyde; HAS; Spectroscopy; Molecular docking Simulation

收稿日期: 2025-01-25 修订日期: 2025-07-13

中图分类号:

O657.3

基金资助: 国家自然科学基金项目（22064005），贵州省重点实验室项目(黔教技[2023]028号)，毕节市科学技术局、贵州工程应用技术学院科学技术联合基金项目(毕科联合[2023]39号)，贵州工程应用技术学院2022年校级质量提升工程项目一流专业-应用化学（ZY202203），大学生创新创业项目（S202310668075，S2024106680701）资助

作者简介: 曾造，1978年生，贵州工程应用技术学院化学工程学院教授 e-mail: 710843449@qq.com

引用本文:

曾造，张浩，樊乙宁，闫金玲. 光谱法和分子对接模拟研究去甲去氢斑蝥酰亚胺缩肉桂醛与人血清白蛋白的相互作用[J]. 光谱学与光谱分析, 2025, 45(10): 2783-2789.
ZENG Zao, ZHANG Hao, FAN Yi-ning, YAN Jin-ling. Study on the Interaction Between Dehydronorcantharidin Imide-Cinnamaldehyde and Human Serum Albumin by Spectroscopy and Molecular Docking Simulation. SPECTROSCOPY AND SPECTRAL ANALYSIS, 2025, 45(10): 2783-2789.

链接本文:

https://www.gpxygpfx.com/CN/10.3964/j.issn.1000-0593(2025)10-2783-07 或 https://www.gpxygpfx.com/CN/Y2025/V45/I10/2783

[1] LIU Fu-long, JIANG Tao, ZUO Dai-shu, et al(刘福龙, 江涛, 左代姝, 等). Chinese Journal of Organic Chemistry(有机化学), 2002, 22(10): 761.
[2] LAN Qing, WU Li, WANG Xian-heng, et al(兰青, 吴丽, 王先恒，等). Chemical Research and Application(化学研究与应用), 2021, 33(5): 786.
[3] Prasad S B, Verma A K. Microscopy and Microanalysis, 2013, 19(6) : 1377.
[4] ZHANG Xue-bo, MA Hang-yu, SUN Teng-da, et al(张学博, 马航宇, 孙腾达, 等). Chinese Journal of Organic Chemistry(有机化学), 2019, 39(3): 2965.
[5] MENG Xiao-hui, HUANG Xu-bo, XIA Zhang-chen, et al(孟晓慧, 黄旭波, 夏张晨, 等). Spectroscopy and Spectral Analysis(光谱学与光谱分析), 2025, 45(1): 107.
[6] ZHOU Su-zhen, XING Li, FAN Jin-bo, et al(周素珍, 邢莉, 范金波, 等). Journal of Chinese Institute of Food Science and Technology(中国食品学报), 2023, 23(2): 61.
[7] Morris G M, Huey R, Lindstrom W, et al. Journal of Computational Chemistry, 2009, 30(16): 2785.
[8] Eberhardt J, Santos-Martins D, Tillack A F, et al. Journal of Chemical Information and Modeling, 2021, 61(8): 3891.
[9] ZENG Zao, LI Jin-hai, SHU Qun-wei, et al(曾造, 李金海, 舒群威, 等). Chemistry Reagents(化学试剂), 2017, 39(11): 1155.
[10] SHI Meng-jie, LI Ze-meng, LU Yong-rui, et al(史梦洁, 李泽萌, 陆勇睿, 等). Chinese Journal of Analysis Laboratory(分析试验室), 2024, 43(3): 340.
[11] SHEN Bing-jun, LIU Ting-ting(申炳俊, 柳婷婷). Chinese Journal of Analytical Chemistry(分析化学), 2020, 48(10): 1383.
[12] WANG Ning, LIU Zhong-ying, HU Xiu-li, et al(王宁, 刘忠英, 胡秀丽, 等). Chemical Journal of Chinese Universities(高等学校化学学报), 2011, 32(2): 241.
[13] Ross P D, Subramanian S. Biochemistry, 1981, 20(11): 3096.
[14] SUN Xiao-yue, BI Shu-yun, WU Jun, et al(孙晓悦, 毕淑云, 吴鋆, 等). Journal of Molecular Science(分子科学学报), 2019, 35(2): 141.
[15] FENG Nan-nan, XIAN Man-kang, DING Xu-hui, et al(冯楠楠, 冼满康, 丁旭辉, 等). Journal of Instrumental Analysis(分析测试学报), 2024, 43(12): 1927.
[16] LU Dong-wei, WU Xiao-yu, XIE Xian, et al(逯东伟, 吴啸宇, 谢宪, 等). Chinese Journal of Luminescence(发光学报), 2017, 38(3): 402.
[17] ZHANG Ai-qin, WANG Man, SHEN Gang-yi, et al(张爱芹, 王嫚, 申刚义, 等). Chemical Journal of Chinese Universities(高等学校化学学报), 2020, 41(9): 2054.
[18] ZENG Zao, SHU Qun-wei, LI Jin-hai(曾造, 舒群威, 李金海). Chemistry[化学通报(中英文)], 2018, 81(1): 83.