臺灣博碩士論文加值系統

在文獻報導香豆素的衍生物被發現具有抗凝血、抗過敏、抗菌等多項醫藥用途。近年來香豆素的衍生物被用於治療愛滋病，學者在研究中發現香豆素衍生物 NSC158393 對愛滋病毒整合脢有良好的抑制活性 (IC50 = 1.5 µM)，本論文依照上述抑制劑的化學結構特性，設計並合成42個具整合脢抑制潛能之香豆素類衍生物。合成方法是用單或雙羥基的苯甲酸與4-羥基苯甲醛進行反應，得到酯類的中間產物，再與4-羥基香豆素進行縮合反應得到最終產物。對合成的42個終產物進行整合脢活性抑制試驗、抑菌及自由基清除試驗。在抗愛滋病毒整合脢的實驗結果顯示化合物5f、5h、6f、6h、6i、6j、13a、13b對整合脢有較佳的抑制作用 (IC50 = 0.9 - 2.6 µM)。在抗菌的實驗中，化合物 5a、5b、6a、6b、6e、15c 對腸球菌 (Entercoccus) 有較佳的抑制效果。在抗自由基實驗中，以化合物 6f、6h、9e效果較好。

It has been reported that coumarin derivatives showed many medical properties, such as anticoagulant, allergic and antimicrobial. Recently, coumarin derivatives has further been applied to the treatment of the AIDS. NSC158393, a coumarin tetramer, has shown potent inhibitory activity (IC50 = 1.5 µM) against HIV-1 integrase. Based on the structural features of the lead compound, we start to design and synthesize 42 compounds with similar structural features. Synthesis to the target compounds was performed starting from mono- or di-hydroxybenzoic acid with 4-hydroxybenzaldehyde, which was converted to a series of ester intermediates. Condensation of the ester intermediates with 4-hydroxycoumarin provided final products. The prepared 42 final products were assayed for HIV-1 inhibition test, anti-bacterial and free radical scavenging tests. Preliminary results showed 5f, 5h, 6f, 6h, 6i, 6j, 13a and 13b possessed good HIV-1 integrase inhibitory activity (IC50 = 0.9 - 2.6 µM). In antibacterial test, 5a, 5b, 6a, 6b, 6e and 15c showed good inhibitory activity against Entercoccus. In free radical scavenging tests, 6f, 6h and 9e showed potent activity.

第一章 緒言
第一節 研究背景……………………………………………………1
壹、香豆素衍生物的用途………………………………………2
貳、愛滋病毒簡介………………………………………………5
參、整合脢簡介…………………………………………………7
肆、整合脢抑制劑簡介…………………………………………10
伍、細胞核卡帕 B因子簡介……………………………………18
第二節 研究方法……………………………………………………22
壹、研究動機……………………………………………………22
貳、合成反應概要………………………………………………27
第二章 材料與方法………………………………………………………29
第一節 試劑及原料…………………………………………………29
第二節 重要儀器……………………………………………………32
第三節 合成實驗部分………………………………………………34
第四節 生物活性試驗………………………………………………86
第三章 結果………………………………………………………………92
第四章 討論………………………………………………………………104
第五章 結論………………………………………………………………113
第六章 參考文獻…………………………………………………………114

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