呋喃咔唑、苯并咪唑異喹啉酮、β-咔啉類衍生物之合成及抗腫瘤活性評估

Synthesis and Antiproliferative Evaluation of Furocarbazole, Benzimidazoisoquinolone, and β-Carboline Derivatives

林柏勝(Bo-Sheng Lin)

指導教授 ： 曾誠齊 ； 楊世群

高雄醫學大學/藥學院/藥學研究所/碩士(2006年)

摘要

本研究主要探討具有DNA嵌入劑結構特徵之furocarbazole、benzimidazoisoquinolone及β-carboline類衍生物的合成與抗腫瘤活性的評估。研究結果發現，細胞毒殺活性主要取決於平面架構的furocarbazole與benzimidazoisoquinolone環上所導入的鹼性側鏈。具有propanylamine取代之furocarbazole衍生物(11d, 12d, 13d)有非常顯著的抗腫瘤活性，在4 μg/mL的濃度時能幾乎100% 抑制MCF-7(乳癌細胞)，NCI-H460(肺癌細胞)，SF-268(中樞神經癌細胞)的生長。Alkylamino取代能提高benzimidazoisoquinolone類衍生物的活性，18c具有最明顯效果。於C-1位置上取代之β-carboline類衍生物則顯示具有較弱的抗腫瘤活性。

關鍵字

嵌入劑, 呋喃咔唑, 苯并咪唑異喹啉酮, β-咔啉

並列摘要

Synthesis and antiproliferative evaluation of furocarbazole, benzimidazoisoquinolone, and β-carboline derivatives with the structural characteristics of DNA-intercalator are described. The results of this study indicate that the cytotoxic effect depends on the basic side chains inserted in the planar nucleus of furocarbazole, and benzimidazoisoquinolone. The propanylamine substituted of furocarbazole derivatives (11d, 12d, 13d), which show the most significant antiproliferative activity on the growth of MCF-7, NCI-H460, and SF-268 at a concentration of 4 μg/mL. The alkylamino substituted side chains of benzimidazoisoquinolone derivatives might facilitate the antiproliferative activity, 18c has particular effect. However, the substituents at position-1 of β-carboline derivatives displayed modest antiproliferative activity.

並列關鍵字

Intercalator ； Furocarbazole ； Benzimidazoisoquinolone ； β-Carboline

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