青蒿琥酯与β-环糊精的键接物及组装聚轮烷的制备和性能研究

发布时间：2018-03-08 02:26

本文选题：β环糊精衍生物　切入点：青蒿琥酯　出处：《昆明理工大学》2014年硕士论文　论文类型：学位论文

【摘要】：环糊精作为一种优秀的药物载体已经被人们广泛研究。环糊精作为载体不仅可以大幅度提高药物的水溶性,相对于其他载体可能还拥有带领药物富集于癌细胞的能力。现在的抗癌药物主要存在水溶性差,靶向性弱等缺点,环糊精基于以上优点,已经成为抗癌药物载体的主要研究对象之一。本文制备了四种6位单取代胺链-β环糊精衍生物载体,并且构筑出相对应的四种叶酸聚轮烷载体。我们选取青蒿琥酯作为活性抗癌药物,将其键接到这一系列环糊精载体及聚轮烷载体上,制备出一个系列的青蒿琥酯-环糊精体系,并对这一体系的结构,性能及体外抗癌活性进行研究。本论文主要由以下三部分组成： 1.制备后续实验所需原料：单-6-对甲苯磺酰-β-环糊精(OTS-βCD),单-6-碘-β-环糊精(I-βCD),单-6-叠氮-β-环糊精(N3-βCD),单-6-氨基-β-环糊精(1N-βCD),单-6-乙二胺-β-环糊精(2N-βCD),单-6-二乙烯三胺-β-环糊精(3N-βCD),单-6-三乙烯四胺-β-环糊精(4N-βCD),同时利用核磁共振谱(1H NMR)对所有产物进行表征。 2.制备四种6位单取代胺链-β环糊精键接物：单-6-青蒿琥酯-氨基-β-环糊精(1NβCD-ATS),单-6-青蒿琥酯-乙二胺-β-环糊精(2NβCD-ATS),单-6-青蒿琥酯-二乙烯三胺-β-环糊精(3NβCD-ATS),单-6-青蒿琥酯-三乙烯四胺-β-环糊精(4NβCD-ATS),采用核磁共振谱(1H NMR)及质谱(MS)对所有产物进行表征。通过XRD, TG, DSC,二维核磁(ROESY)等方法对其性能和结构进行研究,并利用MTT法测定其对LOVO、SW480、HT-29、HCT116四种癌细胞的细胞毒性。 3.构筑四种叶酸聚轮烷键接物：青蒿琥酯单胺轮烷(FA-1NβCD-ATS-PR),青蒿琥酯双胺轮烷(FA-2NβCD-ATS-PR),青蒿琥酯三胺轮烷(FA-3NβCD-ATS-PR),青蒿琥酯四胺轮烷(FA-4NβCD-ATS-PR),采用核磁共振谱(1HNMR)对所有产物进行表征。通过XRD,荧光分光光度计,TG, DSC,二维核磁(ROESY)等方法对其性能和结构进行研究。
[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.
【学位授予单位】：昆明理工大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943;R96

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