臺灣博碩士論文加值系統

本研究主要探討合成6-芳香基茚[1,2-c]喹啉類衍生物與細胞毒活性的評估，將這些化合物以Hep 3B肝癌細胞、Hep G2肝癌細胞、Hep 2.2.1肝癌細胞、A549肺癌細胞、H1299肺癌細胞等五種癌細胞株進行抗增生活性篩選。研究結果發現，6-芳香基茚[1,2-c]喹啉類的衍生物在C-2位置上是F取代基時，可提高對癌細胞的抑制活性；而環上導入叁取代鹼性側鏈之化合物18-20與雙取代的鹼性側鏈之化合物22b與23b可提高對於癌細胞的選擇性與毒殺效果。在環上11號位置導入鹼性側鏈，將導致細胞毒大；如：(E)-2-Fluoro-9-methoxy-6-(4-methoxy- phenyl)-11H-indeno[1,2-c]quinolin-11-one-3-(dimethylamino)propyl oxime (27b)。

This thesis describes the synthesis and cytotoxic evaluation of 6-arylindeno[1,2-c]quinoline derivatives. The synthesized compounds were evaluated for their antiproliferative activities against liver cancers including Hep 3B、Hep G2、Hep 2.2.1 cell lines and lung caners including A549、H1299 cell lines. The results of this study indicated that the introduction of fluoro group at C-2 position significantly enhanced antiproliferative potency. The introduction of basic side chains on the tetracyclic pharmacophore improved selectivity against cancer cells. For examples, the introduction of three basic side chains such as compounds 18-20, and the introduction of two basic side chains such as compounds 22b and 23b enhanced cytotoxicity against cancer cells. Introduction of the basic side chain on the C-11 position have also enhanced cytotoxic effect as the example of (E)-2-fluoro-9-methoxy-6-(4-methoxyphenyl)-11H-indeno- [1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (27b).

中文摘要 ----------------------------------------------------1
英文摘要 ----------------------------------------------------2
壹、緒論 ----------------------------------------------------3
貳、研究動機 ------------------------------------------------13
參、研究方法 ------------------------------------------------22
肆、合成結果與討論
一、6-芳香基茚[1,2-c]喹啉衍生物之合成------------------------26
二、6-芳香基茚[1,2-c]喹啉其11-oxime取代衍生物之合成-----------30
三、茚[1,2-c]喹啉其9-取代衍生物之合成------------------------33
伍、抗癌活性結果討論
ㄧ、6-芳香基茚[1,2-c]喹啉取代衍生物之體外癌細胞抑制百分比------35
二、6-芳香基茚[1,2-c]喹啉其11-oxime取代衍生物之體外癌細胞抑制百
分比-------------------------------------------------39
陸、結論-----------------------------------------------------41
柒、實驗部分
一、溶劑及處理過程 ---------------------------------------43
二、儀器 -------------------------------------------------43
三、試藥 -------------------------------------------------44
四、化合物製備過程 ---------------------------------------47
五、抗癌活性實驗 ----------------------------------------102
捌、參考文獻 -----------------------------------------------104

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