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研究生:蒲家弘
研究生(外文):Chia Hung
論文名稱:1-芳香基取代吡咯[3,2-c]喹啉衍生物作為潛能抗癌試劑
論文名稱(外文):1-Arylpyrrolo[3,2-c]quinoline Derivatives as Potential Anticancer Agents
指導教授:陳香惠
學位類別:碩士
校院名稱:靜宜大學
系所名稱:應用化學研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:99
語文別:中文
論文頁數:74
中文關鍵詞:喹啉抗癌
外文關鍵詞:anticancerquinoline
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本論文主旨是設計與合成1-芳香基吡咯[3,2-c]喹啉衍生物作為潛能抗癌試劑。本實驗室之前以喹啉為骨架,設計1-芳香基取代吡咯[3,2-c]喹啉衍生物,迫使兩芳香環為順式結構,發現此系列化合物對於癌細胞株具有不錯的活性。因此,本論文進一步改變芳香環上的取代基,同樣以合成1-arylpyrrolo[3,2-c]quinoline衍生物為主。將起始物2-acetylbutyrolactone與aniline進行縮合形成中間物,經氯化反應得4-chloro-3-(2-chloroethyl)-2- methylquinoline (1)和其6,8-dimethoxy取代之衍生物2,之後與不同取代基之苯胺及胺基吡啶進行取代反應,得到3-dihydropyrrolo[3,2-c]quinolines (3)和6,8-dimethoxy-2,3-dihydropyrrolo[3,2-c]quinoline (4),最後利用鈀金屬催化劑脫氫,分別得到6和7系列芳香化之標的化合物。合成出之標的化合物均採SRB篩選方式,分別對肺癌細胞株A549、胃癌細胞株AGS及大腸直腸癌細胞株HT-29進行體外細胞毒性測試,發現在苯環上第三位置及第四位置分別接上羥基及甲氧基的化合物3a‧HCl、4a‧HCl、6a針對三種不同的癌細胞株有很高的抑制生長百分比。
This thesis is aimed at design and synthesis of 1-arylpyrrolo[3,2-c]quinoline derivatives as potential anticancer agents. We had been using quinoline ring as skeleton for the design of 1-arylpyrrolo[3,2-c]quinoline derivatives to force the two aromatic rings in cis conformations. Results of in vitro cytotoxicity presumed that this series of compounds have potentials as anticancer drugs. In this study, we change substituent on aryl ring to prepare a series new 1-arylpyrrolo[3,2-c]quinoline derivatives. The synthesis was initiated from the condensation of appropriate aniline and 2-acetylbutyrolactone. After one-pot chlorination, 4-chloro-3-(2-chloroethyl)-2-methyl substituted quinoline (1) and 6,8-dimethoxy derivatives 2 were substituted by various anilines and aminopyridines. Conversion of 2,3-dihydropyrrolo[3,2-c]quinolines (3) and 6,8-dimethoxy-2,3-dihydropyrrolo[3,2-c]quinoline (4) to the fully aromatic system could conveniently be accomplished by dehydrogenation over palladium catalyst to afford target compounds 6 and 7, respectively. All synthesized compounds were subjected to SRB assay for the in vitro cytotoxicity against lung cancer cell lines A549, stomach cancer cell line AGS, and colon cancer cell line HT-29. The results showed that 3-hydroxy-4-methoxy anilino substituted compounds 3a‧HCl, 4a‧HCl and 6a exhibited high inhibitory growth percentage to three cancer cell lines.
第一章 緒論 1
第二章 實驗設計 15
第三章 結果與討論 17
3.1 標的化合物合成 17
3.1.1 4-Chloro-3-(2-chloroethyl)-2-methylquinoline (1) 17
3.1.2 4-Chloro-3-(2-chloroethyl)-6,8-dimethoxy-2-methyl-quinoline (2) 17
3.1.3 1-Aryl-4-methyl-2,3-dihydropyrrolo[3,2-c]quinolines衍生物3及4 18
3.1.4 6,8-Dimethoxy-4-methyl-1-(pyridin-2-yl)-2,3-dihydro-1H-pyrrolo- [3,2-c]quinoline (5) 19
3.1.5 1-Aryl-4-methyl-pyrrolo[3,2-c]quinolines衍生物6及7 20
3.1.6 4-Methyl-1-(pyridin-2-yl)-2,3-dihydro-1H-pyrrolo[3,2-c] quinoline (10) 22
3.2 體外生物活性測試 30
第四章 結論 34
第五章 實驗部份 35
5.1 實驗方法與實驗儀器 35
5.2 試藥、溶劑 35
5.3 合成步驟 36
第六章 參考資料 61
Information Received from the Internet Homepages of the Department of Health, Taiwan, R. O. C. (http://www.doh.gov.tw)
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