臺灣博碩士論文加值系統

喹唑啉(quinazoline)是與苯合成嘧啶雜環的化合物，具有廣泛的藥理活性，例如神經元保護、抗細菌及抗腫瘤等特性，所以對於新藥開發具有很大的潛力。在這項研究中，我們合成一系列新的喹唑啉酮衍生物及抗細胞增生活性評估。首先，將含肟、甲基肟及醯胺之喹唑啉衍生物對三個人類腫瘤細胞株，包括鼻咽癌(NPC-TW01)、血癌(Jurkat)及肺癌(NCI-H226)細胞以MTT-Microculture Tetrazolium進行分析，在這23個衍生物中，5e表現出對鼻咽癌鼻咽癌(NPC-TW01)有最好的抑制活性，其IC50值為4.7 μM。此外，在細胞週期數據中顯示出化合物5e對於鼻咽癌的細胞週期能夠有效滯留在S期。更詳細的細胞週期作用機轉和結構與活性的關係現今正在進行研究中。綜上所敘，5e在新型抗細胞增生藥物中是具有潛力，值得進一步的研究。

The quinazoline (QA) is a heterocyclic compound with benzene fused to pyrimidine and is a well-leading structure for new drug development because it displays a wide spectrum of pharmacological activities such as neuron protective, anti-bacterial and anti-cancer properties. In this study, we have synthesized a series of novel QA derivatives and evaluated their anti-proliferative mechanisms. Firstly, QA series were subjected to MTT assay to examine the growth-inhibitory abilities against three human cancer cell lines, including nasopharyngeal cancer (NPC-TW01), leukemia (Jurkat), and lung carcinoma (NCI-H226). Among 23 compounds, 5e treatment showed dramatic growth-inhibitory effect on NPC-TW01 cells with IC50 of 4.7 μM. Furthermore, cell cycle analysis showed that 5e could cause TW-01 cells arrest in S phase. Detail anti-proliferation mechanisms of 5e against human NPC are actively investigated in our laboratory. In conclusion, 5e is a promising novel anti-proliferation drug and worthy of further investigation.

目錄 ………………………………………………………………………I
圖目錄 ……………………………………………………………………………III
表目錄 ……………………………………………………………………………IV
中文摘要 …………………………………………………………………………V
英文摘要 …………………………………………………………………………VI
誌謝 …………………………………………………………………………VII

第一章 緒論 …………………………………………………………………1
第一節 前言 …………………………………………………………………1
第二節 研究動機與目的 …………………………………………………6
第二章 合成方法與步驟 …………………………………………………10
第一節 合成大綱……………………………………………………………10
第二節 合成步驟與方法 …………………………………………………12
一、3位含肟及甲基肟之喹唑啉衍生物的合成…………………………12
二、3位含醯胺之喹唑啉衍生物5a-e的合成……………………………18
第三章 生物活性評估 …………………………………………………19
第一節 細胞毒活性試驗……………………………………………19
一、實驗方法…………………………………………………………………19
二、初步結果…………………………………………………………………20
三、結果與討論………………………………………………………21
第二節 檢測化合物5e對鼻咽癌(TW-01)細胞週期的影響………25
第四章 實驗部份 …………………………………………………………28
第一節 儀器與試藥…………………………………………………………28
一、儀器 …………………………………………………………………………28
二、試藥 …………………………………………………………………………29
第二節各化合物的製備………………………………………………………30
一、3位含酮的中間產物之喹唑啉酮衍生物的裝備……………………30
二、3-位含肟之喹唑啉酮衍生物的裝備……………………………………36
三、3-位含甲基肟之喹唑啉衍生物的裝備…………………………………42
四、3-位含醯胺之喹唑啉衍生物的裝備……………………………………48
第五章 總結………………………………………………………………53
參考文獻………………………………………………………………………55
研究成果目錄……………………………………………………………………58
A、學會發表論文………………………………………………………………58

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