6-取代啡啶類衍生物之合成及生物活性的評估

Synthesis and Biological Evaluation of 6-Substituted Phenanthridine Derivatives

黃莉芳(Li-Fang Huang)

指導教授 ： 曾誠齊

共同指導教授 ： 陳義龍(Yeh-Long Chen)

高雄醫學大學/生命科學院/醫藥暨應用化學研究所碩士在職專班/碩士(2009年)

摘要

從芸香科植物中萃取出喹啉之生物鹼具有抗癌、抗菌、抗濾過性病毒等生物活性。融入含雜環芳香化合物具有一個平面結構，因這種平面結構能夠嵌入去氧核醣核酸中，以達抑制基因複製的效果，因此本研究主要合成phenanthridine在6位碳原子上含有苯胺及脂肪胺類化合物取代基團並探討其抗細胞增生活性。由實驗結果顯示其對各種癌細胞具有專一性和選擇性，尤其以化合物 N1,N1-dimethyl- N3-(phenanthridine-6-yl)propane-1,3-diamine (37)，和N1-(3,8-dinitrophenanthridin-6-yl)-N2,N2-dimethylethane-12-diamine (46)，和N1-(3,8-dinitrophenanthridin-6-yl)-N3,N3-dimethylpropane-1,3-diamine (47) ，和3,8-dinitro-N-(2-(piperazin-1-yl)ethyl)phenanthridin-6-amine (48) ，3,8-dinitro-6-(piperazin-1-yl)phenanthridine (53)，和 6-(3-methylpiperazin-1-yl)-3,8-dinitrophenanthridine (57)，和 6-(1,4-diazepan-1-yl)3,8-dinitrophenanthridine (58)，和1-(3,8-dinitrophenanthridin-6-yl)piperidin-4-amine (59) ，此八種化合物對乳癌細胞 (MCF-7) 與肺癌細胞 (NCI-H460) 及中樞神經癌細胞 (SF-268) 等都有最佳的活
性，尤其對肺癌細胞 (NCI-H460) 的效果更佳。

關鍵字

啡啶類衍生物

並列摘要

The quinoline alkaloids isolated from the Rutaceae family of plants have various biological activities such as anticancer, antibacterial and antiviral effects. Polycondensed heterocyclic aromatic compounds having a planar structure can intercalate into DNA to inhibit the replication. The derivatives of phenanthridine were synthesized by changing the substitutent at C6, such as aniline group and aliphatic amines, and evaluated for their activities against the growth of various canner cells. Results indicated compounds of N1,N1-dimethyl-N3-(phenanthridine-6-yl)-propane-1,3-diamine (37), N1-(3,8-dinitrophenanthridin-6-yl)-N2,N2-dimethylethane-1,2-diamine (46), N1-(3,8-dinitrophenanthridin-6-yl)-N3,N3-dimethylpropane-1,3-diamine (47), 3,8-dinitro-N-(2-(piperazin-1-yl)-ethyl)phenanthridin-6-amine (48), 3,8-dinitro-6-(piperazin-1-yl)phenanthridine (53), 6-(3-methylpiperazin-1-yl)-3,8-dinitrophenanthridine (57), 6-(1,4-diazepan-1-yl)-3,8-dinitrophenanthridine (58), 1-(3,8-dinitrophenanthridin-6-yl)piperidin-4-amine (59) exhibit good inhibition on the breast cancer cell MCF-7, lung cancer cell NCI-H460 and CNS cancer cell SF-268. These compounds were especiallt active against the growth of lung cancer cell NCI-H460.

並列關鍵字

Phenanthridine

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