臺灣博碩士論文加值系統

本研究與陳健尉老師實驗室合作利用虛擬篩選與體外細胞毒殺實驗得到具有Src蛋白抑制活性之化合物，AC93253與強心配醣體，進一步設計以萘與苯并噻唑分子衍生物作為非小細胞肺癌治療之Src蛋白抑制劑。首先利用醋酸酐催化成功合成化合物AC93253、WY15A10、WY15A30、WY15A40與WY15A60。再利用赫克反應成功與維爾斯邁爾－合成化合物WY15C30。以化合物AC93253、WY15A10、WY15A30、WY15A40、WY15A60、WY15A80、WY15A90及WY15C30進行PC9細胞毒殺實驗，化合物WY15A10在0.01 μM濃度作用72小時的實驗結果顯示PC9細胞存活率小於50%。

Src protein plays a key role in cell division, growth and apoptosis as it is activated at G2/M phase of cell cycle, with induces cell proliferation. When Src protein is overexpressed, abnormal cell proliferation may result in cancer. Taking AC93253 and cardiac glycosides were selected from virtual and in vitro screening. We synthesized compound AC93253, WY15A10, WY15A30, WY15A40 and WY15A60 acetic anhydride as solvent. Compound WY15C30 was synthesized by Heck reaction and Vilsmeier–Haack reaction. Derivatives AC93253, WY15A10, WY15A30, WY15A40, WY15A60, WY15A80, WY15A90 and WY15C30 was treated with PC9 cell line. Compound WY15A10 show good cytotoxicity of PC9 cell line.

中文摘要
英文摘要
第一章 緒論 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 1
第一節 Src蛋白家族 ‥‥‥‥‥‥‥‥‥‥‥ 5
第二節 Src蛋白 ‥‥‥‥‥‥‥‥‥‥‥‥‥ 8
第三節 文獻探討與實驗設計 ‥‥‥‥‥‥‥‥ 11
第二章 實驗材料與方法 ‥‥‥‥‥‥‥‥‥‥‥‥‥ 19
第一節 化學試藥、溶劑與儀器介紹 ‥‥‥‥‥ 19
第二節 Discovery studio 3.1操作 ‥‥‥‥‥‥ 21
第三節 有機合成 ‥‥‥‥‥‥‥‥‥‥‥‥‥ 22
第三章 結果與討論 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 36
第一節 有機合成探討 ‥‥‥‥‥‥‥‥‥‥‥ 37
第二節 生物活性與構效關係探討 ‥‥‥‥‥‥ 68
第四章 結論 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 74
第五章 未來展望 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 76
參考文獻 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 77

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