【摘要】：20(S)-原人參三醇(20(S)-Protopanaxatriol,PPT)是提取于三七、西洋參或人參等植物中人參皂苷元的一種。鑒于其有抗腫瘤,誘導(dǎo)癌細(xì)胞分化的功能,原人參三醇在抗癌藥物的探索研究上有一定的應(yīng)用前景。同時它也有抗疲勞、抗衰老的功效。但是,較低的溶解度限制了其在臨床試驗(yàn)中的應(yīng)用,限制了這種高效藥物的應(yīng)用潛能。因?yàn)榫哂歇?dú)特錐截面空腔結(jié)構(gòu),這種特殊的空腔結(jié)構(gòu)具有“內(nèi)疏水,外親水”的性質(zhì),環(huán)糊精(Cyclodextrin,CD)及其衍生物能夠使難溶性藥物可以在CD空腔的包結(jié)作用下,通過CD良好的水溶性,使藥物達(dá)到增容的效果。這類使藥物增溶的超分子體系的研究,已經(jīng)成為了超分子化學(xué)的一個熱點(diǎn)研究方向。同時,超分子體系能夠使難溶的藥物與小分子白蛋白的研究成為可能,能夠從分子水平剖析藥物在人體內(nèi)作用的過程。對生命科學(xué)的研究也有重要的意義。本文通過合成6種多胺修飾β-CD,與原人參三醇制備成包合物,并研究了原人參三醇超分子體系與牛血清白蛋白(BSA)的相互作用。具體實(shí)驗(yàn)工作如下:1.合成了6種多胺修飾β-CDs(主體1-6),并將其與原人參三醇制備成包合物,分別利用1H NMR、MS、IR、XRD、SEM等方法對它們進(jìn)行表征,通過2D ROESY推測包合物可能的包結(jié)模式;利用紫外滴定計算主客體間的穩(wěn)定常數(shù)并得到1:1的包合比。2.以蛋白質(zhì)作為熒光探針,通過對原人參三醇包合物與BSA相互作用時的熒光光譜研究,了解到原人參三醇超分子體系與BSA結(jié)合過程中,氫鍵和范德華力為主要作用力,BSA的色氨酸殘基上,偶極-偶極非輻射能量轉(zhuǎn)移也會引起B(yǎng)SA的熒光的靜態(tài)猝滅,且多胺修飾β-CD與原人參三醇包合物在一定程度上能引起B(yǎng)SA構(gòu)象的變化。3.通過對主體1/原人參三醇超分子體系對超氧陰離子清除能力的研究,發(fā)現(xiàn)原人參三醇在乙二胺單修飾-β-CD包合增溶后,表現(xiàn)出較好的抗氧化作用。當(dāng)包合物濃度在0.05-0.8mmol/L范圍內(nèi)時,清除能力增長非常明顯,超過0.8mmol/L后趨于平緩,對超氧陰離子濃度的清除能力做到最大,約為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.
【學(xué)位授予單位】：云南師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O641.3;TQ460.1

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