| 摘要: | 根據我們對quinolone類化合物具有抗癌潛力候選藥物的持續研究，結合了2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (K1)、6,7-methylenedioxy-3-phenyl-2-quinolone derivatives及combretastatin A-4 (CA-4)的結構特色，設計了一系列6,7-methylenedioxy-4- substituted phenyl-2-quinolones的衍生物。
首先，先以substituted acetophenones 1a－14a與diethyl carbonate反應得到相對應的ethyl 3-oxo-3-substituted phenylpropanoates 1c－14c。化合物1c－14c再與substituted anilines 1d－3d反應生成相對應的phenylpropanamides 1e－16e，之後再以多聚磷酸 (PPA)進行環化反應得到相對應的標的化合物1f－16f。
將這些標的化合物進行對人類乳癌細胞株MCF-7、人類卵巢癌細胞株2774、SKOV-3、人類白血癌細胞株HL-60、人類肺癌細胞株H460、人類肝癌細胞株Hep 3B、人類腎癌細胞株A498及人類子宮頸癌細胞株CaSki之細胞毒殺活性評估。其中，化合物6,7-methylenedioxy-4-(2,4-dimethoxy)phenyl-2-quinlone (8f) 對人類卵巢癌細胞株SKOV-3、人類白血癌細胞株HL-60、人類肺癌細胞株 H460及人類肝癌細胞株Hep 3B具有顯著的細胞毒殺活性而6,7-methylenedioxy-4-(2,4,6-trimethoxyphenyl)-2-quinolone (12f) 顯示對人類卵巢癌細胞株SKOV-3有顯著的細胞毒殺活性。未來將選擇這兩類化合物做為先導化合物並做進一步的結構修飾。
As part of our continuing investigation of quinolone derivatives as potential and anticancer drug candidates, a series of 6,7-methylenedioxy-4-substituted phenyl-2-quinolones was designed. The design combine structural features of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (K-1), 6,7-methylenedioxy-3-phenyl-2-quinolone derivatives and combretastatin A-4 (CA-4).
Substituted acetophenones 1a－14a were first treated with diethyl carbonate to form the corresponding ethyl 3-oxo-3-substituted phenyl propanoates 1c－14c. Compounds 1c－14c were reacted with substituted anilines 1d－3d to yield the corresponding phenylpropanamides 1e－16e which were subjected to a cyclization reaction in polyphosphoric acid (PPA) to afford the corresponding target compounds 1f－16f.
The synthesized target compounds 1f－16f were evaluated for cytotoxicity against human breast cancer cell MCF7, human ovarian cancer cell 2774 and SKOV-3, human leukemia cell HL-60, human lung cancer cell H460, human hepatoma cell Hep3B, human Cervica cancer cell CaSki. Among them, 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)- 2-quinolone (8f) showed significant cytotoxicity against SKOV-3, HL-60, H460 and Hep 3B cell lines and 6,7-methylenedioxy-4-(2,4,6- trimethoxyphenyl)-2-quinolone (12f) demonstrated significant cytotoxicity against SKOV-3 cell line, these two compounds will be selected as the new lead compounds for further structure modification. |
