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| 題名: | 合成6,7-Methylenedioxy-2-(2,3,4-substituted phenyl)-4-quinolone及其前驅物做為具抗癌潛能之抗癌藥;Synthesis of 6,7-Methylenedioxy-2-(2,3,4-substituted phenyl)-4-quinolone and their Prodrugs as potential anticancer agents |
| 作者: | 范家偉;Chia-Wei Fan |
| 貢獻者: | 中國醫藥大學：藥物化學研究所碩士班 |
| 關鍵詞: | 抗癌;aniticancer |
| 日期: | 2007-07-09 |
| 上傳時間: | 2009-08-13 09:37:29 (UTC+8) |
| 摘要: | 中文摘要
對抗癌藥物而言，微小管無疑是一個重要的作用目標，而持續研究及發展可用作化學治療的抗有絲分裂藥物是刻不容緩的。本研究室將研究目標著重在探討與合成新穎的抗癌製劑，同時發現具有2-phenyl-4-quinolone (2-PQ) 結構的衍生物皆可歸為新一代的抗有絲分裂製劑，而且大部分的衍生物對大多數篩選的細胞株都呈現出良好的抑制活性，在某些動物試驗亦呈現不錯的抗癌效果。這幾年，本研究室亦合成了一系列2-PQ類衍生物，並且從中篩選出一最具代表性，同時擁有優秀抗癌活性的2''-fluoro-6,7-(methylenedioxy)-2-phenyl-4- quinolone (2FMPQ)作為先導化合物。因此，本研究室也著手合成了在2FMPQ之第4位置作取代的相關衍生物，以改善其令人詬病的藥物動力學特質，同時期許相關衍生物在未來可做為前驅藥，順利在人體內轉變成為活性型態。
除此之外，著者以一系列6,7-methylenedioxy-2- (2,3,4-substituted phenyl)-4-quinolone化合物與tubulin之colchicine binding site做docking，並將此一系列類似物在藥理數據的表現，配合其docking在tubulin的活性部位之情形及形成之作用力，做一相關探討與歸納。
Abstract
Microtubules are a valid target for anticancer drugs, and it is necessary to continue developing those antimitotic drugs as chemotherapeutic agents. We put the target on researching and synthesizing novel agents for inhibiting cancer cells in our laboratory. At the same time, we found that 2-phenyl-4-quinolone (2-PQ) derivatives were novel antimitotic agents, and most of them were displayed great anticancer activity at large cell lines and some animal experiment. These years, we synthesized a series of 2-PQ derivatives, and chose one of them with excellent anticancer activity for cancer cells as leading compound, 2''-fluoro-6,7-(methylenedioxy)-2-phenyl-4-quinolone (2FMPQ). Therefore, we synthesized 4-substituted derivatives of 2FMPQ to improve the unsatisfying pharmacokinetic characters of 2FMPQ, and expected they could be prodrugs convert to the active form when they are taken into the body in the future.
We also put the 6,7-methylenedioxy-2-(2,3,4-substituted phenyl)-4-quinolone analogous to dock into the colchicine binding site of tubulin to discuss and conclude the correlation between pharmacological parameter and interactions with protein active domain of the series of substituted 2-PQ. |
| 顯示於類別: | [藥物化學研究所] 博碩士論文
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