線性吲哚喹啉類化合物之合成研究

Studies on the Synthesis of Linear Indoloquinolines

陳盈縉(Ying-Jin Chen)

指導教授 ： 陳義龍

共同指導教授 ： 曾誠齊(Cheng-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(2007年)

摘要

最近我們發現一些4-anilinofuro[2,3-b]quinoline衍生物，像是1-[4-(Furo[2,3-b]quinolin-4-ylamino)-phenyl]ethanone(CIL-102)，(3-chloro-7-methoxyfuro[2,3-b]quinolin-4-ylamino) -phenyl] ethanone (CYL-698)，及ethyl4-(3-chloro-7-methoxyfuro[2,3-b] quinolin- 4-ylamino)benzoate(LHC-2608)具有良好的抗癌活性。更進ㄧ步的探討結構與活性的關係，三環的furo[2,3-b]quinoline置換成四環的cryptotackieine (neocryptolepine)，這是一個indolo[2,3-b]quinoline的生物鹼，且已經被證實為DNA的嵌入劑。此外，indolo[2,3-b]quinoline的4-anilino部分以長碳鏈的側鏈來取代。我們預期這些長碳鏈胺類的取代能在indolo[2,3-b]quinoline插入DNA時與DNA形成氫鍵來增加穩定性。在這些化合物中，化合物53d、 53e、 53g及53h是最具有抗癌活性。

關鍵字

吲哚喹啉

並列摘要

Recently, we have found certain 4-anilinofuro[2,3-b]quinoline derivatives such as 1-[4-(Furo[2,3-b]quinolin-4-ylamino)-phenyl]-
ethanone(CIL-102), (3-chloro-7-methoxyfuro[2,3-b]quinolin-4-ylamino) -phenyl] ethanone(CYL-698), and ethyl4-(3-chloro-7-methoxyfuro[2,3-b] quinolin -4-ylamino)benzoate(LHC-2608) to possess potent anticancer activities. To further explore the structure-activity relationships, the tricyclic furo[2,3-b]quinoline was replaced with cryptotackieine (neocryptolepine), a tetracyclic indolo[2,3-b]quinoline alkaloid which proved to be an effective DNA intercalator. In addition, the 4-anilino moiety of the tetracyclic indolo[2,3-b]quinoline was replaced with aliphatic amino-alkyl side chain. We expect these aliphatic amino-alkyl substituents to form hydrogen bonding with DNA molecule during the intercalation process of tetracyclic indolo[2,3-b]quinoline ring. Among them, compounds 53d, 53e, 53g and 53h were found to possess potent and broad anticancer activities.

並列關鍵字

indoloquinoline

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