臺灣博碩士論文加值系統

合成側鏈為苯胺或苯氧取代的furo[3,2-h]quinolin-8-yl、furo[2,3-h]quinolin-2-yl和 7-prop-2-ynyloxyquinolin-2-yl衍生並評估其抗發炎活性，這些化合物透過將羥基氯化及環化的烷化反應後再與Ar-NH2或Ar-OH反應來合成。抗發炎活性的檢測以這些喹啉衍生物抑制用formyl-methionyl-leucyl-phenylalanine (fMLP, 1 M)和phorbol-12-myristate-13-acetate (PMA, 0.1 M)誘導人類嗜中性白血球產生超氧化物(ROS)的產生效果來評估。
這些化合物的初步檢測結果顯示，抑制fMLP誘導ROS產生的效果優於PMA；呋喃[2,3-h]喹啉衍生物比起相對應的呋喃[3,2-h]喹啉更有效力。而呋喃[2,3-h]喹啉衍生物中又以1-[4-(8-methylfuro[2,3-h]quinolin-2-ylamino)phenyl]ethanone (12a)對於抑制fMLP誘導ROS產生的效果最佳，IC50值為1.08 M。這些化合物並沒有顯著的細胞毒性，且可能發展成抗發炎製劑治療因氧化壓力導致之疾病。結構與活性間的詳細機轉正在進ㄧ步的研究中。

Certain aniline- or phenoxy-substituted furo[3,2-h]quinolin-8-yl, furo[2,3-h]quinolin-2-yl, and 7-prop-2-ynyloxyquinolin-2-yl derivatives were synthesized and evaluated for their anti-inflammatory activities. These compounds were synthesized via alkylation of hydroxyl precursors followed by the chlorination, cyclization, and reaction with appropriate Ar-NH2 or Ar-OH. Anti- inflammatory activities of these quinoline derivatives were evaluated on the suppression of reactive oxygen species (ROS) production induced by formyl-methionyl-leucyl-phenylalanine (fMLP, 1 M) and phorbol-12-myristate-13-acetate (PMA, 0.1 M) in human neutrophils.
The preliminary assays indicated that these compounds were more effective in the inhibition of ROS production induce by fMLP than that of PMA, and furo[2,3-h]quinolines were more potent than their corresponding furo[3,2-h]quinoline isomers. For the furo[2,3-h]quinolines, 1-[4-(8-methylfuro[2,3-h]quinolin-2-ylamino)phenyl]ethanone (12a) was the most potent for the inhibition of fMLP-induced ROS production with an IC50 value of 1.08 M. These compounds have the potential to be novel anti-inflammatory agents for the treatment of oxidative stress-induced disease with no significant cytotoxicity. The detail mechanisms and structure-activity relationships are active investigated now.

目 錄

中文摘要……………………………………………………………………Ⅰ
英文摘要……………………………………………………………………Ⅱ
目錄…………………………………………………………………………Ⅲ



第一章 緒論…………………………………………………………………1
第一節 前言………………………………………………………………1
第二節 背景與目的…………………………………………………8
第二章 合成方法與步驟…………………………………………………11
一、 Furo[2,3-h]quinoline及其衍生物的合成……………10
二、 Furo[3,2-h]quinoline及其衍生物的合成……………13
第三章 生物活性評估……………………………………………………15
第一節 抗發炎試驗…………………………………………………15
第二節 抗癌活性檢測…………………………………………………15
第三節結果與討論…………………………………………………16
第四章 實驗部份…………………………………………………………20
第一節 儀器與試藥………………………………………………………20
一、 儀器………………………………………………………………20
二、 試藥………………………………………………………………21
第二節 各化合物的製備…………………………………………………22
第五章 結論………………………………………………………………48
參考文獻……………………………………………………………………49

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