新穿心莲内酯/β-环糊精包合物的分子结构及抗增殖作用研究

doi:10.5246/jcps.2023.06.036

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (6): 427-434.DOI: 10.5246/jcps.2023.06.036

• 【研究论文】 • 下一篇

新穿心莲内酯/β-环糊精包合物的分子结构及抗增殖作用研究

赵炎葱¹, 王丽¹, 曾静静², 李景华²^,^*()

1. 河南大学第一附属医院, 河南开封 475001
2. 河南大学天然药物与免疫工程重点实验室, 河南开封 475004

收稿日期:2022-11-14 修回日期:2022-12-23 接受日期:2023-02-20 出版日期:2023-07-01 发布日期:2023-07-01
通讯作者: 李景华
作者简介:
+ Tel.: +86-13693894529, E-mail: lijinghua@henu.edu.cn
基金资助:
The National Natural Science Foundation of China (Grant No. 81373974); Projects of Science and Technology of Henan Province (Grant No. 222102310671); Key Scientific Research Projects in Henan Colleges and Universities (Grant No. 22A350012); and the Kaifeng Technology Development Plan (Grant No. 1403132).

The structure and antiproliferative activity of the inclusion complex of neoandrographolide/β-cyclodextrin

Yancong Zhao¹, Li Wang¹, Jingjing Zeng², Jinghua Li²^,^*()

1 The First Affiliated Hospital, Henan University, Kaifeng 475001, China
2 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, China

Received:2022-11-14 Revised:2022-12-23 Accepted:2023-02-20 Online:2023-07-01 Published:2023-07-01
Contact: Jinghua Li

摘要/Abstract

摘要：

本文通过实验和理论方法研究了新穿心莲内酯/β-CD包合物的分子结构和抗增殖作用; 采用微波辅助饱和溶液法制备了新穿心莲内酯/β-CD包合物。通过紫外可见光谱测定了包合物的平衡常数, 通过DTA、IR和分子模拟技术对配合物的结构进行了表征和确证。结果表明: 新穿心莲内酯能够进入β-CD空腔形成包合物, 新穿心莲内酯/β-CD包合物表现出与新穿心莲内酯不同的光谱特征和性质。包合物分子比例是1:1, 新穿心莲内酯分子的五元内酯环从β-CD较宽的边缘被包合在它的空腔中。包合物的平衡常数为489.9918 mol/L。通过包合处理, 新穿心莲内酯的体外抗增殖活性亦显著提高。环糊精类包合是目前医药行业中提高药物生物利用度较成功的做法之一。

关键词: 一, 新穿心莲内酯, β-环糊精, 平衡常数, 包合物, 分子模拟, 抗增殖活性研究

Abstract:

In the present study, the inclusion complex of neoandrographolide and β-cyclodextrin (β-CD) was studied by experimental and theoretical methods. The inclusion complex of neoandrographolide/β-CD was prepared by the saturated solution method. The equilibrium constant of the inclusion complex was determined by UV-vis spectra. The structure of the complex was characterized by DTA, FT-IR, and molecular modeling techniques. All these results indicated that neoandrographolide could enter the cavity of β-CD to form an inclusion complex, and the neoandrographolide/β-CD inclusion complex exhibited different spectroscopic features and properties from neoandrographolide. The molar rate of the inclusion complex was 1:1. The five-membered lactone ring of the neoandrographolide molecule was inserted into the cavities of β-CD from the wider edge. The calculated equilibrium constant of the complex was 489.9918 mol/L. The in-vitro antiproliferative activity of neoandrographolide was significantly improved through the inclusion complexation process. Taken together, the inclusion complexation process was a successful method that could be used in the pharmaceutical industry.

Key words: Neoandrographolide, β-Cyclodextrin, Equilibrium constant, Inclusion complex, Molecular modeling, Antiproliferative activity studies

Supporting:

赵炎葱, 王丽, 曾静静, 李景华. 新穿心莲内酯/β-环糊精包合物的分子结构及抗增殖作用研究[J]. 中国药学(英文版), 2023, 32(6): 427-434.

Yancong Zhao, Li Wang, Jingjing Zeng, Jinghua Li. The structure and antiproliferative activity of the inclusion complex of neoandrographolide/β-cyclodextrin[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(6): 427-434.

图/表 8

Figure 1. Chemical structure of neoandrographolide.

Figure 2. Chemical structure of β-CD.

Figure 3. DTA curves of (1) β-CD, (2) neoandrographolide, (3) their physical mixture, and (4) inclusion complex.

Figure 4. Infrared spectrogram of (A) β-CD, (B) neoandrographolide, (C) their physical mixture, and (D) the inclusion complex.

Figure 5. Regression curve equation.

Table 1. The interaction energy between neoandrographolide and β-CD calculated with CAChe 6.1 software.

Figure 6. Diagram of computer simulation.

Table 2. In vitro activity of neoandrographolide and inclusion complex.

参考文献 16

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新穿心莲内酯/β-环糊精包合物的分子结构及抗增殖作用研究

The structure and antiproliferative activity of the inclusion complex of neoandrographolide/β-cyclodextrin

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