本研究主要探討具有DNA 嵌入劑結構特徵之benzimidazoisoquinoline、pyrazoloquinoline 及isoxazoloquinoline 衍生物的設計、合成以及抗增生活性評估。其中在抗增生活性結果中發現,2,5-disubsituted-benzimidazole 衍生物26d,對於Huh-7(肝癌細胞)具有最有效的抑制效果。 另外我們還成功合成出pyrazoloquinoline 及isoxazoloquinoline衍生物,並在其C-4 上做不同取代基的苯胺修飾,以提高化合物對各種不同癌細胞的抑制活性與選擇性。
This thesis describes synthesis and antiproliferative evaluation of certain potential DNA intercalating agents such as benzimidazoisoquinoline, pyrazoloquinoline, and isoxazoloquinoline. Among them, compound 26d which is one of the 2,5-disubsituted benzimidazole dertivatives, possessed the most potent antiproliferative activity against human liver cancer cell (Huh-7) with an IC50 value of 6.21 μM. We have also synthesized the derivatives of pyrazoloquinoline and isoxazoloquinoline,with an aim to improve the selectivity and specificity of the compounds against the growth of various cancer cells.