臺灣博碩士論文加值系統

合成含醯胺之3,4-二氫喹啉酮衍生物並且評估它們生物的活性。這些化合物是由芳香環的酚氫氧基先進行烷化反應，接著再與
疊氮化鈉進行Schmidt反應。
從抗癌的初步篩選分析中，以衍生物中N-(naphthalene-2-yl)- 2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yloxy)acetamide (6a)對於台灣本土鼻咽癌(NPC-TW01)和血癌(Jurkat 和Molt-4)能夠有效的抑制癌細胞生長，其IC50值分別為0.57， 0.24，和 0.36 μM。N-(biphenyl-4-yl)- 2-(2-oxo-1,2,3,4-tetrahydroquinolin-6-yloxy)acetamide (6e)化合物對於肝癌細胞特別具有顯著的細胞毒性，其IC50值為2.83 μM。
在細胞週期分析數據中顯示出6a衍生物對於血癌細胞能夠有效的滯留在S期，但隨著時間的延長將滯留在Sub-G1期。詳細的細胞週期作用機轉和結構與活性的關係現今正在進行研究中。

Certain amide-containing 3,4-dihydroquinolin-2(1H)-one derivatives
were synthesized and evaluated for their biological activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the reaction with NaN3(Schmidt reaction).
From the preliminary assays, N-(naphthalene-2-yl)-2-(2-oxo-1,2,3,4- tetrahydroquinolin-6-yloxy)acetamide (6a) was the most potent with IC50 values of 0.57, 0.24, and 0.36 μM against the growth of NPC-TW01 (nasopharyngeal carcinoma), Jurkat and Molt-4 (leukemia), respectively. For the Hep3B (hepatoma), N-(biphenyl-4-yl)-2-(2-oxo-1,2,3,4-tetrahydroquino- lin-6-yloxy)acetamide (6e) exhibited significant cytotoxicity with IC50 value of 2.83 μM. The cell cycle analysis data showed that Jurkat cells were significantly arrested at S phase for a short period treatment; prolong treatment will significant increased sub-G1 population. The detail cytotoxicity mechanisms and structure-activity relationships are active investigated now.

中文摘要……………………………………………………………………Ⅰ
英文摘要……………………………………………………………………Ⅱ
誌謝…………………………………………………………………………Ⅲ
目錄………………………………………………………………………Ⅳ
圖目錄……………………………………………………………………Ⅵ
表目錄……………………………………………………………………Ⅶ

第一章 緒論…………………………………………………………………1
第一節 前言…………………………………………………………………1
第二節 研究動機與目的……………………………………………………5
第二章 合成方法與步驟…………………………………………………8
第一節 合成大綱…………………………………………………………8
第二節 合成方法與步驟…………………………………………………11
一、 6位含醯胺之3,4-二氫喹啉酮衍生物6 a-6e的合成………………11
二、 7位含醯胺之3,4-二氫喹啉酮衍生物11 a-11e的合成……………13
三、 8位含醯胺之3,4-二氫喹啉酮衍生物16 a-16e的合成……………15
第三章 生物活性評估……………………………………………………19
第四章 實驗部份…………………………………………………………31
第一節 儀器與試藥………………………………………………………31
一、儀器……………………………………………………………………31
二、試藥……………………………………………………………………32
第二節 抗血小板凝集活性試驗…………………………………………33
ㄧ、實驗方法………………………………………………………………33
第三節 細胞毒活性試驗…………………………………………………36
ㄧ、實驗方法………………………………………………………………36
第四節 各化合物的製備…………………………………………………37
一、6-位含醯胺之3,4-二氫喹啉酮衍生物(6 a-e)的製備 ……………… 37
二、7-位含醯胺之3,4-二氫喹啉酮衍生物(11 a-e)的製備……………… 42
三、8-位含醯胺之3,4-二氫喹啉酮衍生物(16 a-e)的製備……………… 47
第五章 總結………………………………………………………………52
參考文獻…………………………………………………………………… 55
研究成果目錄………………………………………………………………57
A、學會發表論文……………………………………………………………57

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