呋喃[3,2-c]喹啉與呋喃[2,3-b]喹啉衍生物之合成及生物活性的研究

Synthesis and Biological Evaluation of Furo[3,2-c]quinoline and Furo[2,3-b]quinoline Derivatives

賴心嫺(Hsin-Hsien Lai)

指導教授 ： 曾誠齊

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2006年)

摘要

三環口夫口南[2,3-b]口奎口林構型對於生物活性上的天然物是很重要的架構，例如：dictamnine, acrophylline, confusameline, skimmianine, kokusaginine, 和haplopine等。這些生物鹼有廣泛的生物特性，包含抗過敏（anti-allergic）、抗發炎（anti-inflammatory）、細胞毒性（cytotoxic）以及抗血小板凝集（antiplatelet aggregation）和阻斷鈣離子通道（voltage-gated potassium channel blocking）的活性。由於口夫口南[2,3-b]口奎口林的衍生物具有廣泛地生物用途，我們以合成一系列有關直線型的口夫口南[2,3-b]口奎口林的衍生物，並評估其4位碳原子上以不同環狀胺基的修飾時，以探討其抗腫瘤增生的活性。為了評估此類構效關係（SAR），我們也合成了一系列角型的口夫口南[3,2-c]口奎口林的衍生物，其為直線型的口夫口南[2,3-b]口奎口林的同分異構物。初步細胞生長活性抑制的分析，發現所有合成的化合物在4 μg/ml濃度時，對於MCF-7（乳癌細胞）、NCH460（肺癌細胞）、SF268（中樞神經癌細胞）的生長沒有抑制效果。關於它們在抗發炎和抗血小板的生物活性我們也將持續進行探討中。

關鍵字

抗發炎 ； 呋喃[3,2-c]喹啉 ； 呋喃[2,3-b]喹啉

並列摘要

The tricyclic furo[2,3-b]quinoline skeleton constitutes an important group of bioactive natural products such as dictamnine, acrophylline, confusameline, skimmianine, kokusaginine, and haplopine. These alkaloids were found to possess wide-ranging biological properties including anti-allergic, anti-inflammatory, cytotoxic, antiplatelet aggregation, and the voltage-gated potassium channel blocking activities. Due to the biological versatility of furo[2,3-b]quinoline derivatives, we have synthesized a number of linear furo[2,3-b]quinoline derivatives with cyclic amino moiety substituted at C-4 position for antiproliferative evaluation. In order to establish structure-activity relationship (SAR), we have also synthesized certain isomeric angular furo[3,2-c]quinoline derivatives for comparison. The preliminary assay indicated these compounds did not significantly inhibit the growth of MCF7, NCI-H460, and SF-268 at a concentration of 4 μg/ml. Their anti-inflammatory and anti-platelet activities will also be evaluated.

並列關鍵字

anti-inflammatory ； Furo[3,2-c]quinoline ； Furo[2,3-b]quinoline

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