茚[1,2-b]喹啉衍生物之合成及生物活性評估

Synthesis and Biological Evaluation of Indeno[1,2-b]quinoline Derivatives

林明楠(Ming-Nan Lin)

指導教授 ： 陳義龍

共同指導教授 ： 曾誠齊(Cherng-Chyi Tzeng)

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2008年)

摘要

本研究主要探討具有DNA嵌入劑結構特徵之茚[1,2-b]喹啉類衍生物的合成與抗腫瘤活性的評估。研究結果發現，細胞毒殺活性主要取決於茚[1,2-b]喹啉的平面骨架與環上所導入的鹼性側鏈。而環上的10號與11號位置是決定抗增生活性關鍵位置，其中具有aminoalkoxyimino取代之10-methyl-11H-indeno[1,2-b]quinolin-11-one O-aminoalkyl oxime (8c-h)，11-oxo-11H-indeno[1,2-b]quinoline-10-carbaldehyde O-aminoalkyl oxime (14d-j)，11H-indeno[1,2-b]quino-line-10-carbaldehyde O-aminoalkyl oxime (20a-e)，衍生物有非常顯著的抗腫瘤活性，在4 μg/mL的濃度時能幾乎100% 抑制MCF-7 (乳癌細胞)，NCI-H460 (肺癌細胞)，SF-268 (中樞神經癌細胞)的生長。

關鍵字

茚[1,2-b]喹啉嵌入劑 ； 細胞毒 ； 抗增生

並列摘要

Synthesis and antiproliferative evaluation of 11H-indeno[1,2-b]quinoline derivatives with the structural characteristics of DNA intercalator are described. The results of this study indicate that the cytotoxic effect depends on the basic side chains that substituted in the planar nucleus of 11H-indeno[1,2-b]quinoline. Substituents at C-10 and C-11 positions are crucial to the antiproliferative potency of 11H-indeno[1,2-b]quinoline, the aminoalkoxyimino substitutent of10-methyl-11H-indeno[1,2-b]quinolin-11-one (8c-h), 11-oxo-11H-indeno[1,2-b]quinoline-10-carbaldhyde (14d-j),11H-indeno[1,2-b]quinoline-10-carbaldehyde derivatives (20a-e), which show the most significant antiproliferative activity on the growth of MCF-7, NCI-H460, and SF-268 at a concentration of 4 μg/mL.

並列關鍵字

indeno[1,2-b]quinoline ； intercalator ； cytotoxic ； antiproliferative

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