几种多胺修饰环糊精与原人参三醇超分子体系的研究

发布时间：2018-07-25 20:37

【摘要】：20(S)-原人参三醇(20(S)-Protopanaxatriol,PPT)是提取于三七、西洋参或人参等植物中人参皂苷元的一种。鉴于其有抗肿瘤,诱导癌细胞分化的功能,原人参三醇在抗癌药物的探索研究上有一定的应用前景。同时它也有抗疲劳、抗衰老的功效。但是,较低的溶解度限制了其在临床试验中的应用,限制了这种高效药物的应用潜能。因为具有独特锥截面空腔结构,这种特殊的空腔结构具有“内疏水,外亲水”的性质,环糊精(Cyclodextrin,CD)及其衍生物能够使难溶性药物可以在CD空腔的包结作用下,通过CD良好的水溶性,使药物达到增容的效果。这类使药物增溶的超分子体系的研究,已经成为了超分子化学的一个热点研究方向。同时,超分子体系能够使难溶的药物与小分子白蛋白的研究成为可能,能够从分子水平剖析药物在人体内作用的过程。对生命科学的研究也有重要的意义。本文通过合成6种多胺修饰β-CD,与原人参三醇制备成包合物,并研究了原人参三醇超分子体系与牛血清白蛋白(BSA)的相互作用。具体实验工作如下:1.合成了6种多胺修饰β-CDs(主体1-6),并将其与原人参三醇制备成包合物,分别利用1H NMR、MS、IR、XRD、SEM等方法对它们进行表征,通过2D ROESY推测包合物可能的包结模式;利用紫外滴定计算主客体间的稳定常数并得到1:1的包合比。2.以蛋白质作为荧光探针,通过对原人参三醇包合物与BSA相互作用时的荧光光谱研究,了解到原人参三醇超分子体系与BSA结合过程中,氢键和范德华力为主要作用力,BSA的色氨酸残基上,偶极-偶极非辐射能量转移也会引起BSA的荧光的静态猝灭,且多胺修饰β-CD与原人参三醇包合物在一定程度上能引起BSA构象的变化。3.通过对主体1/原人参三醇超分子体系对超氧阴离子清除能力的研究,发现原人参三醇在乙二胺单修饰-β-CD包合增溶后,表现出较好的抗氧化作用。当包合物浓度在0.05-0.8mmol/L范围内时,清除能力增长非常明显,超过0.8mmol/L后趋于平缓,对超氧阴离子浓度的清除能力做到最大,约为52%。
[Abstract]:20 (S)-Protopian triol (PPT) is a kind of ginsenoside extracted from Panax notoginseng, Panax quinquefolium, Panax ginseng and so on. In view of its function of anti-tumor and inducing cancer cell differentiation, propanaxtriol has a certain application prospect in the exploration and study of anticancer drugs. At the same time, it also has anti-fatigue, anti-aging effect. However, low solubility limits its use in clinical trials and limits the potential of this highly effective drug. Because of its unique cone-section cavity structure, this special cavity structure has the property of "internal hydrophobic, external hydrophilic". Cyclodextrin (CD) and its derivatives can make insoluble drugs under the inclusion of CD cavity. Through the good water solubility of CD, the drug can achieve the effect of compatibilization. The study of this kind of supramolecular system for drug solubilization has become a hot research direction in supramolecular chemistry. At the same time, the supramolecular system can make it possible to study the insoluble drugs and small molecular albumin, and to analyze the process of drug action in human body at the molecular level. The study of life science is also of great significance. In this paper, six kinds of polyamines modified 尾 -CD were synthesized to form inclusion compounds with proto-panaxatriol, and the interaction between procyclotriol supramolecular system and bovine serum albumin (BSA) (BSA) was studied. The specific experimental work is as follows: 1. Six kinds of polyamines modified 尾 -CDs (main body 1-6) were synthesized, and the inclusion compounds were prepared with proto-panaxyl alcohol. They were characterized by 1H NMRM ROESY, and the possible inclusion modes of the inclusion complexes were deduced by 2D ROESY. The stability constant between host and guest was calculated by ultraviolet titration and the inclusion ratio of 1:1 was obtained. By using protein as a fluorescence probe, the fluorescence spectra of procanaxtriol inclusion complex interacting with BSA were studied, and the process of BSA binding of proto-ginsenotriol supramolecular system was found out. Hydrogen bond and van der Waals force are the main forces on the tryptophan residue of BSA. The dipole-dipole non-radiation energy transfer also leads to the static quenching of BSA fluorescence. The polyamine modified 尾 -CD inclusion compound with procanaxel can induce the conformation change of BSA to a certain extent. Through the study of the superoxide anion scavenging ability of the supramolecular system of main 1 / proto-ginsenotriol, it was found that propanaxtriol showed a better antioxidant effect after the solubilization of 尾 -CD with ethylenediamine mono-modified. When the concentration of the inclusion compound is in the range of 0.05-0.8mmol/L, the scavenging ability of the inclusion compound is very obvious, and the scavenging ability of superoxide anion is about 52 when the concentration of superoxide anion is higher than that of 0.8mmol/L.
【学位授予单位】：云南师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O641.3;TQ460.1

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