本文選題：β環(huán)糊精衍生物　切入點(diǎn)：青蒿琥酯　出處：《昆明理工大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：環(huán)糊精作為一種優(yōu)秀的藥物載體已經(jīng)被人們廣泛研究。環(huán)糊精作為載體不僅可以大幅度提高藥物的水溶性,相對(duì)于其他載體可能還擁有帶領(lǐng)藥物富集于癌細(xì)胞的能力�，F(xiàn)在的抗癌藥物主要存在水溶性差,靶向性弱等缺點(diǎn),環(huán)糊精基于以上優(yōu)點(diǎn),已經(jīng)成為抗癌藥物載體的主要研究對(duì)象之一。本文制備了四種6位單取代胺鏈-β環(huán)糊精衍生物載體,并且構(gòu)筑出相對(duì)應(yīng)的四種葉酸聚輪烷載體。我們選取青蒿琥酯作為活性抗癌藥物,將其鍵接到這一系列環(huán)糊精載體及聚輪烷載體上,制備出一個(gè)系列的青蒿琥酯-環(huán)糊精體系,并對(duì)這一體系的結(jié)構(gòu),性能及體外抗癌活性進(jìn)行研究。本論文主要由以下三部分組成： 1.制備后續(xù)實(shí)驗(yàn)所需原料：?jiǎn)?6-對(duì)甲苯磺酰-β-環(huán)糊精(OTS-βCD),單-6-碘-β-環(huán)糊精(I-βCD),單-6-疊氮-β-環(huán)糊精(N3-βCD),單-6-氨基-β-環(huán)糊精(1N-βCD),單-6-乙二胺-β-環(huán)糊精(2N-βCD),單-6-二乙烯三胺-β-環(huán)糊精(3N-βCD),單-6-三乙烯四胺-β-環(huán)糊精(4N-βCD),同時(shí)利用核磁共振譜(1H NMR)對(duì)所有產(chǎn)物進(jìn)行表征。 2.制備四種6位單取代胺鏈-β環(huán)糊精鍵接物：?jiǎn)?6-青蒿琥酯-氨基-β-環(huán)糊精(1NβCD-ATS),單-6-青蒿琥酯-乙二胺-β-環(huán)糊精(2NβCD-ATS),單-6-青蒿琥酯-二乙烯三胺-β-環(huán)糊精(3NβCD-ATS),單-6-青蒿琥酯-三乙烯四胺-β-環(huán)糊精(4NβCD-ATS),采用核磁共振譜(1H NMR)及質(zhì)譜(MS)對(duì)所有產(chǎn)物進(jìn)行表征。通過XRD, TG, DSC,二維核磁(ROESY)等方法對(duì)其性能和結(jié)構(gòu)進(jìn)行研究,并利用MTT法測(cè)定其對(duì)LOVO、SW480、HT-29、HCT116四種癌細(xì)胞的細(xì)胞毒性。 3.構(gòu)筑四種葉酸聚輪烷鍵接物：青蒿琥酯單胺輪烷(FA-1NβCD-ATS-PR),青蒿琥酯雙胺輪烷(FA-2NβCD-ATS-PR),青蒿琥酯三胺輪烷(FA-3NβCD-ATS-PR),青蒿琥酯四胺輪烷(FA-4NβCD-ATS-PR),采用核磁共振譜(1HNMR)對(duì)所有產(chǎn)物進(jìn)行表征。通過XRD,熒光分光光度計(jì),TG, DSC,二維核磁(ROESY)等方法對(duì)其性能和結(jié)構(gòu)進(jìn)行研究。
[Abstract]:As an excellent drug carrier, cyclodextrin has been widely studied. Compared with other carriers, cyclodextrins may also have the ability to lead the drug enrichment in cancer cells. The current anticancer drugs mainly have the disadvantages of poor water solubility and weak targeting. Cyclodextrin is based on the above advantages. In this paper, four kinds of 6-position monosubstituted amine chain 尾 -cyclodextrin derivatives were prepared. We selected artesunate as active anticancer drug and connected it to these series of cyclodextrin carriers and polyrotane carriers to prepare a series of artesunate cyclodextrin system. The structure, properties and anticancer activity of the system in vitro were studied. 1. Preparation of raw materials for follow-up experiments: mono-6- p-toluenesulfonyl- 尾 -cyclodextrin (Ots- 尾 CDN), mono-6-iodo- 尾 -cyclodextrin (I- 尾 CDT), mono-6-azido 尾 -cyclodextrin (N3- 尾 CDN), mono-6-amino-beta-cyclodextrin (1N- 尾 CDN), mono-6-ethylenediamide- 尾 -cyclodextrin (2N- 尾 CDN), mono-6-diethylenediamide- 尾 -cyclopaste (Mono-6-diethylenediamide- 尾 -cyclodextrin). All the products were characterized by 1H-NMRs and 3N- 尾 -CDO, 4N- 尾 CDO, single -6-triethylenetetraamine- 尾 -cyclodextrin, respectively. 2. Preparation of four 6-position monosubstituted amines-尾 -cyclodextrin bonds: mono-6-artesunate amino-beta-cyclodextrin 1N 尾 CD-ATSN, mono-6-artesunate -ethylenediamide- 尾 -cyclodextrin 2N 尾 CD-ATSs, mono-6-artesunate diethylenetriamide- 尾 -cyclodextrin 3N 尾 CD-ATSN, mono-6-artesunate -diethyltriamide- 尾 -cyclodextrin 3N 尾 CD-ATSN, monoartesunate -2-ethylenedienediamide- 尾 -cyclodextrin. All the products were characterized by 1H NMR and MS. The properties and structures of the products were studied by means of XRD, TG, DSCand 2D NMR, ROESY. The cytotoxicity of LOVOA SW480 HT-29HCT116 cells was determined by MTT assay. 3. Four kinds of folic acid polyrotane bond junctions were constructed: artesunate monoamine rotorane FA-1N 尾 CD-ATS-PRN, artesunate diamine-rotorane FA-2N 尾 CD-ATS-PRP, artesunate triaminohexane FA-3N 尾 CD-ATS-PRS-PRN, artesunate tetraamide-FA-4N 尾 CD-ATS-PRS-PRN, and all the products were characterized by 1HNMRs. The performance and structure of XRD, fluorescence spectrophotometer (TG, DSC, 2D NMR) were studied.
【學(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R943;R96

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