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研究生:許雅淑
研究生(外文):Ya-Shu Hsu
論文名稱:利用電腦分子模擬研究吡唑喹啉衍生物作為p38αMAPK抑制劑
論文名稱(外文):The study of pyrazolo[4,3-c]quinoline derivatives as inhibitor of p38α MAPK by computer molecular modeling
指導教授:曾誠齊
指導教授(外文):Cherng-Chyi Tzeng
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:醫藥暨應用化學研究所碩士在職專班
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:175
中文關鍵詞:電腦分子模擬唑喹衍生物
外文關鍵詞:p38α MAPK inhibitorspyrazolo[43-c]quinoline derivatives
相關次數:
  • 被引用被引用:0
  • 點閱點閱:126
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本研究主要是希望藉由Accerlys Discovery studio分子模擬的軟體以本實驗室已合成的吡唑喹啉衍生物來分析、修飾並找出新的抗發炎藥物p38α MAPK inhibitors,研究結果找出十三個具有潛力的化合物,預測其活性與藥效基團,並且與已發表有活性的化合物作比較,以驗證此軟體對分子模擬找出的化合物其結構與活性的真實性。在過去研究報告中顯示典型的p38α MAPK inhibitors與標的蛋白質(1A9U)氫鍵鍵結的有三個amino acid(Met109 H-bond binding, Thr106 hydrophobic pocket, Lys53 H-bond binding)來顯示其活性外,經由1A9U的protein與ligand docking找出第四個amino acid即Asp168的H-bond binding(acceptor and donor),藉由第四點的聯結,可望提高活性,使得化合物與活性口袋的箝制更緊密,藥效更強,抑制效果更好。
This study analyses and modifies the model of Accerlys Discovery Studio with the pyrazolo[4,3-c]quinoline derivatives as inhibitor of p38α MAPK by computer molecular modeling. From this study we intend to find novel molecule to be potential anti-infection P38 MAPK inhibitors. The results of this study led to the discovery of 13 possible compounds which we have further predict their activities and the pharmacophore. Although preious studies suggested three amino acids involved in the interaction of typical p38α MAPK inhibitors, we have found the forth amino acid which was also involved. Through chemical binding of the forth amino acid, the inhibitory activity was further promoted.
中文摘要.................................................1
英文摘要.................................................2
壹、前言.................................................3
貳、研究動機.............................................9
參、研究方法............................................22
一、吡唑喹啉衍生物作不同部位官能基的分子對接............22
二、已合成具有活性的化合物的分子對接....................56
三、預測已合成化合物的藥效基團的活性...................121
四、預測最佳的化合物和藥效基團的活性...................128
五、預測預估化合物最好的活性...........................131
六、已合成化合物的藥效基團.............................138
七、p38α inhibitors 第四點amino acid( Asp168) 的化合物..158
八、化合物的合成途徑...................................164
肆、 結論..............................................166
伍、 參考文獻..........................................170
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