設計及合成苯胺基取代吡唑喹啉衍生物

Design and Synthesis of Anilino-Substituted Pyrazoloquinoline Derivatives

凃柏丞(Po-Cheng Tu)

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(2012年)

https://doi.org/10.6832/KMU.2012.00030

摘要

吖啶（acridine），尤其是以9-苯胺吖啶（9-anilinoacridines）的衍生物最受到關注，是因其有可崁入至DNA的能力，進而抑制拓樸異構酶二型（topoisomerase II, topo II ）。而我們也已經合成及評測4-anilinofuro[2,3-b]quinoline衍生物的抗癌活性，其結構是以9-苯胺吖啶（9-anilinoacridines）為基礎而將原先的苯環以呋喃環取代。1-[4-(furo[2,3-b]quinolin- 4-ylamino)phenyl]ethanone（CIL-102）於美國國家癌症研究中心（NCI）對於60株不同癌細胞進行篩選，發現其mean graph midpoint （GI50）為0.025μM，而(E)-1-(4- (furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone O-2-aminoethyl oxime （CYW-1865）對NCI-H460肺癌細胞有很好的選擇抑制性，其graph midpoint（GI50）為0.63μM。
本研究合成anilinopyrazolo[3,4-b]quinoline衍生物可視為將CIL-102及CYW-1865的呋喃環以吡唑環取代。同分異構物anilinopyrazolo[4,3-c]quinoline也已經準備對於抗癌活性進行評測。

關鍵字

苯胺基 ； 吡唑喹啉

並列摘要

Acridine derivatives, especially 9-anilinoacridines have been extensively studied as potential chemotherapeutic agents due to their capability of intercalating DNA leading to the inhibition of mammalian topoisomerase II. Recently, we have synthesized and evaluated anticancer activities of 4-anilinofuro[2,3-b]quinoline derivatives which can be structurally related to 9-anilinoacridines by isosteric substitution of a benzene moiety for a furan ring. Among them, 1-[4-(furo[2,3-b]quinolin- 4-ylamino)phenyl]ethanone (CIL-102) exhibited a broad spectrum of antiproliferative activity, with a meangraph midpoint (GI50) of 0.025 ?嵱, in the NCI’s full panel of 60 human cancer cells while (E)-1-(4- (furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone O-2-aminoethyl oxime (CYW-1865) was selectively active against the growth of NCI-H460 with a GI50 of 0.63 ?嵱. This thesis describes the synthesis of anilinopyrazolo[3,4-b]quinoline derivatives which can be considered as isosteric isomers of CIL-102 and CYW-1865 in which the furan moiety was replaced with a pyrazole ring. The isomeric anilinopyrazolo[4,3-c]quinoline derivatives have also been prepared for anticancer evaluations.

並列關鍵字

Anilino-Substituted ； Pyrazoloquinoline

參考文獻

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