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研究生:陳民祥
研究生(外文):Min-Hsiang Chen
論文名稱:異黃酮衍生物的合成與活性評估
論文名稱(外文):Synthesis and Biological Evaluation of Isoflavone Derivatives
指導教授:陳意莉
指導教授(外文):I-Li Chen
學位類別:碩士
校院名稱:大仁科技大學
系所名稱:製藥科技研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:46
中文關鍵詞:合成異黃酮抗癌類黃酮腫瘤幹細胞
外文關鍵詞:SynthesisIsoflavoneFlavoneTumor stem cellAnticancer
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在植物化學中異黃酮和黃酮類化合物是一普遍存在的族群,它們具有廣泛及多樣化的生物活性,包括抗腫瘤、抗骨質疏鬆症、抗發炎、抗血小板凝集、抗真菌感染及抗氧化等。為了建立結構與活性間的關係,我們合成出了若干個異黃酮與黃酮類衍生物,並評估他的生物活性。將7-羥基黃酮、7-羥基異黃酮及4’-羥基-7-羥基異黃酮分別與不同胺類在甲醛溶液中進行Mannich反應,分別得到具有不同的胺烷基取代的產物。我們期待這些目標產物比起天然類黃酮化合物在藥理活性上更具有選擇性。
初步篩選的結果,這些化合物對於乳癌(MCF-7)、肺癌 (NCI-H460)、中樞神經癌(SF-286)、非小細胞肺癌(NCI H-661)、台灣鼻咽癌(NPC-tw01)和T淋巴癌細胞(Jurkat)等六株癌細胞均沒有細胞毒性。因此,這些異黃酮衍生物在未來中,將進行抗骨質疏鬆與抗血小板凝集的活性評估。
Isoflavonoids (3-phenyl-4H-1-benzopyran-4-one) and flavonoids (2-phenyl-4H-1-benzopyran-4-one) are ubiquitous families of phytochemicals that possess a wide variety of biological effect with include anticancer, anti-osteoporosis, anti-inflammation, antiplatelet aggregation , antifungal and anti-oxidative activities. To investigate structural features with respect to the biological properties and to establish structure-activity relationships (SAR), we have synthesized a number of isoflavone and flavone derivatives for biological evaluation. Thus, 7-hydroxyflavone, 7-hydroxyisoflavone, and 4’,7-dihydroxyisoflavone respectively were treated with various amines and formalin (Mannich reaction) to give their respective aminoalkyl products. We expect these target compounds to be more selective in pharmacology than the natural flavonoids.
Preliminary assays indicated that these compounds were non-cytotoxic against six cancer cells including MCF-7 (breast cancer), NCI-H460 (non-small cell lung cancer), SF-286 (CNS cancer), H661 (Lung carcinoma), NPC-tw01(NPC) and Jurkat (T leukemia Jurkat). Thus, these isoflavone derivatives will be evaluated for their anti-osteoporotic and anti-platelet activities in the future.
中文摘要……………………………………………………………Ⅰ
英文摘要………………………………………………………………Ⅱ
誌謝……………………………………………………………………III
目錄…………………………………………………………………….IV

第一章 緒論……………………………………………………………1
第一節 前言……………………………………………………………1
第二節 研究動機與目的………………………………………………7
第二章 合成方法與步驟………………………………………………14
(一) 7-羥基異黃酮衍生物5a至5e的合成…………………………14
(二) 4’-羥基-7-羥基異黃酮衍生物9a至9e的合成………………16
(三) 7-羥基黃酮衍生物11a至11e的合成…………………………18
第三章 細胞毒活性驗…………………………………………………19
第一節 實驗方法與初步結果……………………………………… 19
第二節 結果與討論………………………………………………… 23
第四章 實驗部份………………………………………………………24
第一節 儀器與試藥……………………………………………………24
一、儀器…………………………………………………………………24
二、試藥…………………………………………………………………25
第二節 各化合物的製備………………………………………………26
一、7-Hydroxy-3-phenyl-4H-chromen-4-one (4)之製備………………26
二、7-Hydroxy-8-((4-methylpiperazin-1-yl)methyl)-3-phenyl-4H-chrome-
n-4-one (5a)之製備…………………………………………………27
三、7-Hydroxy-3-phenyl-8-(pyrrolidin-1-ylmethyl)-4H-chromen-4-one (5b) 之製備……………………………………………………… 28
四、7-Hydroxy-3-phenyl-8-(piperidin-1-ylmethyl)-4H-chromen-4-one (5c) 之製備………………………………………………………………29
五、7-Hydroxy-8-(morpholinomethyl)-3-phenyl-4H-chromen-4-one (5d)
之製備……………………………………………………………30
六、7-Hydroxy-8-((isopropylamino)methyl)-3-phenyl-4H-chromen-4-one (5e)之製備…………………………………………………………31
七、7-Hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one (8)之製
備…………………………………………………………………32
八、8-(ethoxymethyl)-7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4
-one (9a)之製備………………………………………………33
九、7-Hydroxy-3-(4-hydroxyphenyl)-8-(pyrrolidin-1-ylmethyl)-4H-chro-
men-4-one (9b)之製備 ………………………………………… 34
十、7-Hydroxy-3-(4-hydroxyphenyl)-8-(piperidin-1-ylmethyl)-4H
-chromen-4-one (9c)之製備…………………………………35
十一、7-Hydroxy-3-(4-hydroxyphenyl)-8-(morpholinomethyl)-4H-chrom-
en-4- one (9d)之製備…………………………………………… 36
十二、7-Hydroxy-3-(4-hydroxyphenyl)-8-((isopropylamino)methyl)-4H-
chrom-en-4-one (9e)之製備……………………………………37
十三、7-Hydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-
chromen-4-one (11a) 之製備…………………………………38
十四、7-Hydroxy-2-phenyl-8-(pyrrolidin-1-ylmethyl)-4H-chromen-4-one
(11b) 之製備………………………………………………39
十五、7-hydroxy-2-phenyl-8-(piperidin-1-ylmethyl)-4H-chromen-4-one (11c) 之製備……………………………………………………40
十六、7-Hydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen-4-one
(11d)之製備…………………………………………………… 41
十七、7-Hydroxy-8-((isopropylamino)methyl)-2-phenyl-4H-chromen
-4-one (11e) 之製備……………………………………42
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