4-苯胺呋喃[2,3-b]喹啉類衍生物之烷基化及抗增生活性的評估

Synthesis and Antiproliferative Evaluation of N-Alkyl-4-anilinofuro[2,3-b]quinoline Derivatives

許雅惠(Shiu Ya Huei)

指導教授 ： 楊世群

高雄醫學大學/藥學院/藥學研究所/碩士(2011年)

摘要

本研究利用天然生物鹼白鮮鹼(dictamine)三環呋喃喹啉 (furoquinoline)衍生物為骨架，在4-苯胺呋喃[2,3-b]喹啉(4-anilinofuro[2,3-b]quinoline) 4-C上進行修飾，數據指出，1-[4-(呋喃[2,3-b]喹啉-4-氨基)-苯基]乙酮(1-[4-(furo[2,3-b]quinoline- 4-ylamino)-phenyl]ethanone) (CIL-102, 1) (GI50 = 0.025 μM)及3-氯- 4-[(4-甲氧基苯基)氨基]呋喃[2,3-b]喹啉(3-chloro-4- [(4-methoxyphenyl)-amino]furo[2,3-b]quinoline) (CIL-378, 2) (GI50 = 0.025 μM)在抗腫瘤細胞增生表現出色且優於以上市藥物柔紅黴素(daunomycin)，但水溶解度低與其無選擇性的細胞毒性，是需克服的問題。本研究主要在4-苯胺呋喃[2,3-b]喹啉4-C上氮進行烷基化修飾，且進行其抑制腫瘤細胞增生活性的探討與評估，並提升在水中的溶解度及更好抑制癌細胞選擇性，進一步證明其為有效抗增生藥物。

關鍵字

苯胺呋喃喹啉白鮮鹼 ； 甲基碘 ； 乙基碘

並列摘要

The skeleton of natural dictamnine alkaloid belongs to a tricyclic furoquinoline derivative. Previous reports indicated that the introduction of a suitable substituent at the 4-position of furoquinoline ring afforded certain potential antiproliferative agents. For examples, 1-[4-(furo[2,3-b]quinoline-4-ylamino)phenyl]ethanone (1, GI50 = 0.025 μM) and 3-chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline (2, GI50 = 0.025 μM) exhibited more potent antiproliferative activities than the clinically used anticancer drug, daunomycin. However, poor water solubility and general cytotoxicities exhibited by both compounds 1 and 2 prompted extensive structural optimizations to overcome these problems. This thesis describes the synthesis and antiproliferative evaluation of certain N-alkyl 4-anilinofuro[2,3-b]quinoline derivatives with an aim to obtain novel furoquinoline derivatives with a high water solubility as well as a better selective anticancer activity. Certain N-alkyl 4-anilinofuro[2,3-b]quinoline derivatives were successfully synthesized and proved to be potential antiproliferative agents.

並列關鍵字

anilinofuroquinoline ； dictamine ； iodomethane ； iodoethane

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