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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳昭岑 | |
| dc.contributor.author | Yu-Ching Chou | en |
| dc.contributor.author | 周育晴 | zh_TW |
| dc.date.accessioned | 2021-06-17T02:13:26Z | - |
| dc.date.available | 2023-01-04 | |
| dc.date.copyright | 2018-01-04 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-11-30 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68145 | - |
| dc.description.abstract | 發展對癌細胞具高度選擇性的抗癌藥物，解決化療藥物具嚴重副作用的問題，為許多研究團隊努力的目標。本論文發展具光活化性質的抗癌前驅藥物，選用高熱穩定度且吸收波長較長的二噻吩乙烯作為光調控開關，修飾上臨床癌症治療使用的氮芥類DNA烷化劑與具拉電性的吡啶鎓離子，合成出Py-F6DTE-Mus-c與NAEPy-F6DTE-Mus-c兩個分子。
由水解速率測試證實，Py-c與NAEc皆可經由近紅外光的激發開環形成活性較高的Py-o與NAE-o。透過圓二色光譜法，探討Py-o、Py-c、NAE-o與NAE-c對DNA二級結構造成的影響，結果顯示合環狀態的Py-c與 NAE-c會對DNA的二級結構有較明顯的影響。此外利用凝膠電泳實驗進一步比較分子在照射近紅外光前後對DNA進行烷基化的能力差異，實驗結果顯示Py-c與 NAE-c在經過近紅外光活化後將有較高的活性對DNA進行烷化。以上研究結果顯示Py-c與NAE-c有成為光活化藥物的潛力，。然而，從細胞毒性實驗結果來看，NAE-o、NAE-c與經近紅外光活化之NAE-c對MCF-7的毒性差異不大，而細胞屬於相對複雜的系統，因此，未來研究方向應更進一步解析NAE-c、NAE-o與細胞作用時的相關機制。 | zh_TW |
| dc.description.abstract | Development of highly selective anticancer drugs toward tumor cells in order to resolve the severe side effects caused by chemotherapeutic drugs is a primary goal for many research groups. The thesis is aimed to develop a photoactived anticancer prodrug. Incorporation of the aniline mustard, a clinical DNA alkylator, as well as electrophilic pyridinium to the dithienylethene (DTE) core was achieved by multistep synthesis to afford Py-F6DTE-Mus-c and NAEPy-F6DTE-Mus-c. Development of highly selective anticancer drugs toward tumor cells in order to resolve the severe side effects caused by chemotherapeutic drugs is a primary goal for many research groups. The thesis is aimed to develop a photoactived anticancer prodrug. Incorporation of the aniline mustard, a clinical DNA alkylator, as well as electrophilic pyridinium to the dithienylethene (DTE) core was achieved by multistep synthesis to afford Py-F6DTE-Mus-c and NAEPy-F6DTE-Mus-c. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T02:13:26Z (GMT). No. of bitstreams: 1 ntu-106-R04223147-1.pdf: 6872091 bytes, checksum: bc7bcc8ec959048f91ac5af6a6c6a2de (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 目錄
目錄 Ⅰ 圖目錄 Ⅲ 表目錄 Ⅸ 簡稱用語對照表 Ⅹ 中文摘要 Ⅻ 英文摘要 XIV 第一章 緒論 1 1-1 癌症的治療 1 1-2 光活化藥物療法 (photopharmacology) 介紹 2 1-2-1 激發光源的波長選擇 2 1-2-2 光控制分子開關 (photoswitch) 3 1-2-2-1 偶氮苯 (azobenzene) 3 1-2-2-2 螺噁嗪 (spirooxazines) 和螺吡喃 (spiropyrans) 5 1-2-2-3 二噻吩乙烯 (dithieylethene) 5 1-2-3 結合光控制分子開關的前驅藥物 6 1-3 去氧核醣核酸與癌症治療 10 1-3-1 去氧核醣核酸的簡介 10 1-3-2 去氧核醣核酸複製之機轉與抗癌藥物 11 1-4 DNA烷化劑在癌症治療上的應用及發展 14 1-4-1 順鉑類 (cisplatin) 化合物 14 1-4-2 醌甲基類 (Quinone methide) 化合物 19 1-4-3 氮芥子氣類 (N-mustard) 化合物 21 1-4-4 結合活性調控基團的DNA烷化劑 25 第二章 設計與合成具光活化性質之氮芥類烷化劑 28 2-1 相關研究回顧 28 2-2 分子設計概念 31 2-3 NAEPy-F6DTE-Mus-c的逆合成與合成介紹 34 2-4 NAEPy-F6DTE-Mus-c的性質研究與討論 42 2-4-1 NAEPy-F6DTE-Mus-c的光物理性質 42 2-4-2 NAEPy-F6DTE-Mus-c照光前後的水解活性測試與分子電荷分布計算 44 2-4-3 NAEPy-F6DTE-Mus-c與 Py-F6DTE-Mus-c之水溶性差異比較 47 第三章 DNA烷化與細胞實驗結果 51 3-1 與DNA序列作用後的圓二色光譜分析 51 3-2 凝膠電泳分析 55 3-3 細胞毒性測試 67 3-4 總結 68 實驗部分 71 Ⅰ. 一般敘述 71 Ⅱ 實驗步驟及光譜數據 73 Ⅲ DNA反應以及圓二色光譜與凝膠電泳分析 86 參考文獻 89 附錄 94 | |
| dc.language.iso | zh-TW | |
| dc.subject | 去氧核醣核酸 | zh_TW |
| dc.subject | 烷化劑 | zh_TW |
| dc.subject | 二?吩乙烯 | zh_TW |
| dc.subject | 光活化 | zh_TW |
| dc.subject | DNA | en |
| dc.subject | Dithienylethene | en |
| dc.subject | Photoactivated | en |
| dc.subject | Alkylator | en |
| dc.title | 發展具光活化性質之氮芥類抗癌前驅藥物應用於選擇性烷化去氧核醣核酸 | zh_TW |
| dc.title | Development of Photoactivated Nitrogen Mustard Anticancer Prodrug Aiming to Selectively Alkylate DNA | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳進庭,冀宏源 | |
| dc.subject.keyword | 烷化劑,去氧核醣核酸,二?吩乙烯,光活化, | zh_TW |
| dc.subject.keyword | Alkylator,DNA,Dithienylethene,Photoactivated, | en |
| dc.relation.page | 101 | |
| dc.identifier.doi | 10.6342/NTU201704426 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-11-30 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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