新型二萜内酯化合物Euphorikanin A的结构和性质计算分析

doi:10.3964/j.issn.1000-0593(2025)02-0371-08

摘要
参考文献
相关文章 (15)

全文: PDF (4526 KB)
输出: BibTeX | EndNote (RIS)

摘要：化合物Euphorikanin A是从甘遂大戟根中分离出的新型二萜内酯化合物，初步生物活性发现其具有肿瘤细胞毒活性，分析药物的结构、光谱性质和成药可能性是了解其生物活性的必要前提，也可为开发新药提供参考。运用密度泛函理论B3LYP/6-311++G(2d, p)和ωB97XD/6-311++G(2d, p)方法，对化合物Euphorikanin A的药效构象、几何和电子结构、红外(IR)、紫外-可见(UV-Vis)、核磁共振(NMR)谱进行计算，并借助概念密度泛函理论进行分子全局反应指数分析，使用药物代谢动力学平台开展成药性和ADME/Tox评估。计算结果显示Euphorikanin A有唯一药效构像，两种方法和不同溶剂环境中化合物几何结构参数值相近，计算值与晶体参数吻合较好。理论红外光谱特征与实验吻合，水环境中计算的IR光谱更接近真实环境，理论计算校正因子为0.94。Euphorikanin A紫外光谱最大吸收峰在193.88～201.75 nm。两种方法得到的核磁数据理论结果与实验吻合度高，R²均大于0.94。Euphorikanin A的六元环的羟基可能为反应活性位点。Euphorikanin A的全局反应参数和药代动力学表现出良好性能，尤其在Caco-2细胞膜通透性、血脑屏障透过率和人肠道吸收性。Euphorikanin A的结构和性质在成药性拥有优势，具有进一步开发的价值。

关键词：Euphorikanin A；密度泛函理论；电子结构；反应指数；成药性

Abstract：Euphorikanin A, a recently discovered diterpene lactone compound is dated from the roots of Euphorbia reausui, exhibits promising tumor cytotoxic activity. To comprehend its biological effects fully, it is imperative to investigate its structural characteristics, spectral properties, and potential as a therapeutic agent. Consequently, further examination of its structure and properties can serve as a valuable resource for advancing novel pharmaceuticals. The density functional theory B3LYP/6-311++G (2d, p) and ωB97XD/6-311++G (2d, p) methods were applied to calculate the pharmacophoric conformation, geometric and electronic structure, infrared (IR), ultraviolet-visible (UV-Vis), nuclear magnetic resonance (NMR) spectra of the compound Euphorikanin A, and the molecular global reaction index analysis was carried out by using conceptual density functional theory. The pharmacokinetics platform was used to evaluate druggability and ADME/Tox. The calculation results showed that Euphorikanin A has a unique pharmacophoric conformation, and the geometric structure parameters of the compound were similar in both methods and different solvent environments. The calculated values were in good agreement with the crystal parameters. The theoretical infrared spectral characteristics are consistent with the experiment, and the calculated infrared spectra in the water environment are closer to the real values, with a theoretical scaling factor of 0.94. The maximum absorption peak of Euphorikanin A in the UV-Vis spectrum is between 193.88 and 201.75 nm. The theoretical results of the nuclear magnetic data obtained by both methods agree well with the experimental results, with R² greater than 0.94. The hydroxyl group of the six-membered ring of Euphorikanin A may be the reaction's active site. The compound's global reaction parameters and pharmacokinetics showed good performance, especially regarding Caco-2 cell membrane permeability, blood-brain barrier permeability, and human intestinal absorption. The structure and properties of Euphorikanin A have advantages in druggability and are worthy of further development.

Key words：Euphorikanin A; Density functional theory; Electronic structure; Reaction index; Druggability

收稿日期: 2023-07-25 修订日期: 2024-04-15

中图分类号:

O641.3

基金资助: 国家自然科学基金项目(21177098)和浙江省自然科学基金项目(LY16B070006)资助

通讯作者: 王朝杰 E-mail: chjwang@wmu.edu.cn

作者简介: 徐佳禛，女，1993年生，嘉兴学院附属第二医院主管药师 e-mail: xujiazhen0529@163.com

引用本文:

徐佳禛，王长江，王朝杰. 新型二萜内酯化合物Euphorikanin A的结构和性质计算分析[J]. 光谱学与光谱分析, 2025, 45(02): 371-378.
XU Jia-zhen, WANG Chang-jiang, WANG Chao-jie. Theoretical Study on the Structure and Properties of a Novel Diterpenoid Lactone Compound Euphorikanin A. SPECTROSCOPY AND SPECTRAL ANALYSIS, 2025, 45(02): 371-378.

链接本文:

https://www.gpxygpfx.com/CN/10.3964/j.issn.1000-0593(2025)02-0371-08 或 https://www.gpxygpfx.com/CN/Y2025/V45/I02/371

[1] Shamkant B B. Journal of Ethnopharmacology, 2014, 151(1): 733.
[2] Carla C K, Talissa L, Luiza S C, et al. Revista Brasileira de Farmacognosia, 2017, 27(2): 206.
[3] Bruno R M, Bruna M L, Aline S J, et al. Journal of Ethnopharmacology, 2016, 191(15)：29.
[4] LI Xiao-jing(李晓静). Chinese Journal of Medicinal Chemistry(中国药物化学杂志), 2012, 22(3): 1.
[5] Paul A W, Kee J M, Warrington J M. Science, 2008, 320(5876): 649.
[6] LI Nan-qi, XU Wen-wen, TANG Yang, et al(李楠琦, 徐雯雯, 汤洋, 等). Chinese Journal of Pain Medicine(中国疼痛医学杂志), 2020, 26(9): 8.
[7] MA Li, MENG Xian-hua, YANG Jun-li(马丽，孟宪华，杨军丽). Natural Product Research and Development(天然产物研究与开发), 2022, 34: 699.
[8] Fei D Q, Dong L L, Qi F M, et al. Organic Letters, 2016, 18(12): 2844.
[9] Shi L L, He Y D, Gong J X, et al. Chemical Communications, 2020, 56: 531.
[10] Moritz J C, Markus N A B, Remo R, et al. Journal of the American Chemical Society, 2021, 143(22): 8261.
[11] Chen Z, Zhao K, Jia Y. Angewandte Chemie International Edition, 2022, 61(16): 1.
[12] Gen F, Kandemirli S G, Kandemirli F. Acta Chimica Sinica, 2021, 68(2): 320.
[13] Liu Y G, Xu J J, Han L, et al. Interdisciplinary Sciences: Computational Life Sciences, 2021, 13(1): 1.
[14] LIANG Xiao-rui, CONG Jing-xian, LI Yin, et al(梁小蕊，丛静娴，李荫，等). Spectroscopy and Spectral Analysis(光谱学与光谱分析), 2023, 43(5): 1381.
[15] FU Rong, LU Tian, CHEN Fei-wu(付蓉, 卢天, 陈飞武). Acta Physico-Chimica Sinica(物理化学学报), 2014, 30(4): 12.
[16] HUANG Luo-yi, WENG Yue-yue, HUANG Xu-hui(黄罗仪, 翁约约, 黄旭慧). Chemical Journal of Chinese Universities(高等学校化学学报), 2021, 42(9): 14.
[17] Frisch M J, Trucks G W, Schlegel H B, et al. Gaussian 16 (Gaussian, Inc., Wallingford CT, 2016).
[18] Lu T, Chen F W. Journal of Computational Chemistry, 2012, 33: 580.
[19] Zhang J, Lu T. Physical Chemistry Chemical Physsics, 2021, 23: 20323.
[20] Lipinski C A. Drug Discovery Today, 2004, 1(4): 337.
[21] YI Ping-gui, ZHANG Zhi-yu, TAO Hong-wen, et al(易平贵，张志于，陶洪文, 等). Journal of Atomic and Molecular Physics(原子与分子物理学报), 2020, 37(1): 8.
[22] ZOU Jian-wei, ZHANG Bing, HU Gui-xiang，et al(邹建卫, 张兵, 胡桂香, 等). Acta Chimica Sinica(化学学报), 2004, 62(3): 241.
[23] LÜ Xin-xin, XU Jia-zhen, LI Zheng-xue, et al(吕鑫鑫, 徐佳禛, 李郑雪, 等). Journal of Advances in Physical Chemistry(物理化学进展), 2016, 5(1): 9.
[24] CHEN Meng-yi, SUN Xiang, HUANG Luo-yi(陈蒙仪，孙祥，黄罗仪). Journal of Wenzhou Medical University(温州医科大学学报), 2021, 51(9): 10.