臺灣博碩士論文加值系統

天然物查耳酮文獻中顯示具有多種生物活性。由於查耳酮在植物中容易取得和合成，所以查耳酮衍生物的研究備受關注。另一方面，喹啉為骨架的衍生物，多篇文獻中也顯示具有抗增生活性。本論文主要探討合成喹啉查爾酮的衍生物與抗增生活性的評估。其中以3-(4-取代苯基)喹啉-2-醛與不同取代的芳香酮進行醛酮縮合進而合成出3-苯基取代喹啉查爾酮之衍生物時具有不錯的產率。這些新合成的化合物，針對肺癌細胞(A549、H1299和H460)，乳腺癌細胞(MCF-7、MB-231和SKBR-3)，與正常細胞(MRC-5與M10)進行抗增生活性評估。其中(E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (19c)對H1299和SKBR-3的IC50值分別為0.71和0.52μM，而對照藥物topotecan（其IC50值> 10.0μM在兩株癌細胞中）。更值得注意的是化合物19c顯示對MB-231乳癌細胞的選擇性最高，IC50值小於0.10μM，對正常細胞M10則無細胞毒IC50值9.38μM。

Chalcones are natural products which have displayed a wide variety of biological activities. Due to their abundance in plants and ease of synthesis, studies on chalcone derivatives have attracted much attention. On the other hand, quinoline skeleton is one of the key building elements for a large number of biologically active compounds. Therefore, the present thesis describes the preparation of certain chalcone derivatives in which an aryl moiety was replaced with quinoline nucleus. These newly synthesized 3-phenylquinolinylchalcone derivatives were evaluated in vitro against a panel of six cancer cell lines including three non-small cell lung cancer cells (H1299, H460, and A549), three breast cancer cells (MCF-7, MDA-MB-231, and SKBR-3), and a normal mammary epithelial cell (M10). Among them, (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl
)quinolin-2-yl)prop-2-en- 1-one (19c) was active against the growth of H1299 and SKBR-3 with IC50 values of 0.71 and 0.52μM respectively which was more active than the positive topotecan (IC50 values of > 10.0μM in each case). Compound 19c was also active against the growth of MDA-MB-231 with an IC50 value of less than 0.10μM and was not cytotoxic to the normal mammary epithelial cell (M10) with an IC50 value of 9.38μM.

中文摘要----------------------------------------------------------------------------------1
英文摘要----------------------------------------------------------------------------------2
壹、序論------------------------------------------------------------------------------------3
貳、研究動機----------------------------------------------------------------------------14
参、研究方法----------------------------------------------------------------------------29
肆、合成結果與討論-------------------------------------------------------------------31
伍、抗癌活性與結果討論-------------------------------------------------------------42
陸、結論----------------------------------------------------------------------------------52
柒、實驗部份----------------------------------------------------------------------------55
一、溶劑及處理過程-----------------------------------------------------------55
二、儀器、試劑製備與來源-----------------------------------------------------55
三、試藥---------------------------------------------------------------------------56
四、各化合物製備過程----------------------------------------------------------59
捌、參考文獻---------------------------------------------------------------------------130
附錄-------------------------------------------------------------------------------------139

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