吲哚[3,2-c]喹啉類衍生物之合成及生物活性評估

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

陳麒安(Chi-An Chen)

指導教授 ： 陳義龍

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

11H-indolo[3,2-c]quinoline是藉由氮原子將2-phenylnaphthalene與quinoline結合成共平面四環的多融合雜環芳香化合物，部分的化合物且已被證實為DNA嵌入劑並具有抗增生活性；而環上的6號與11號位置是決定抗增生活性的關鍵位置；因此，在本文我們分別在6號與11號位上合成不同的取代基團並探討其抗增生活性評估。最後結果顯示4-(11H-Indolo[3,2-c]quinolin-6-ylamino)phenol (33b), 3-(11H- Indolo[3,2-c]quinolin-6-ylamino)phenol (33c), and dimethyl-[11- (2-morpholin-4-ylethyl)-11H-Indolo[3,2-c quinolin-6-yl]amine (42)此三種化合物有最佳的活性；其中化合物33c與42分別對肺癌細胞(NCI-H460)與乳癌細胞(MCF-7)的TI值為7.20和7.62。

關鍵字

DNA嵌入劑

並列摘要

11H-Indolo[3,2-c]quinoline is a coplanar tetracyclic heterocycle in which the consisting 2-phenyl group and quinoline moieties are conformationally locked through a nitrogen bridge. A number of 11H-Indolo[3,2-c]quinoline derivatives have been proved to possess DNA-intercalating and antiproliferative activities. Substituents at C-6 and C-11 positions are crucial to the antiproliferative potency of 11H-Indolo[3,2-c]quinoline derivatives. Therefore, we have synthesized certain 11H-Indolo[3,2-c]quinolines with different substituents at C-6 and C-11 positions for antiproliferative evaluation. Results indicated 4-(11H-Indolo[3,2-c]quinolin-6-ylamino)phenol (33b), 3-(11H-Indolo[3,2-c] quinolin-6-ylamino)phenol (33c), and dimethyl-[11-(2-morpholin- 4-ylethyl)-11H-Indolo[3,2-c]quinolin-6-yl]amine (42) are three of the most active. The selective index (SI) for normal cell and cancer cell are 7.20 (NCI-H460) and 7.62 (MCF-7) respectively for 33c and 42.

並列關鍵字

11H-indolo[3,2-c]quinoline

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