【作者】 刘晓月；

【导师】 吴平；

【作者基本信息】 浙江大学 ， 生物化学与分子生物学， 2006， 硕士

【摘要】 有毒植物中包含各种具有生物活性多样的化合物和结构复杂的次生代谢物，是寻找抗肿瘤药物的丰富资源。本论文采用四甲基偶氮唑盐（MTT）酶还原法，对四十一种有毒植物进行了初步的抗肿瘤活性体外测定。并从中发现了一枝黄花属植物加拿大一枝黄花（Solidago canadensis L.）具有明显的体外抗肿瘤活性。其花序的石油醚和乙酸乙酯粗提物在对五株肿瘤细胞的体外抑制实验中，表现出了广谱的抗肿瘤效应，半数抑制率IC₅₀均低于50μg／ml，并具有明显的量效关系。采用生物活性跟踪法，对加拿大一枝黄花乙酸乙酯粗提物进行分离纯化后，获得两个具有较强抗肿瘤活性的同分异构体二萜化合物，二者结构经核磁综合手段确定为当归酰氧基克拉文酸（angeloyloxykolavenic acid）和巴豆酰氧基克拉文酸（tigloyloxykolavenic acid）。 论文首次发现这两个二萜化合物具有广谱的抗癌活性，在体外对红白血病K562，肝癌SMMC 7721，乳腺癌Bcap 37和MCF-7，子宫颈癌Hela，肺腺癌SPC-Al，结肠癌SW620等七株肿瘤细胞的生长抑制能力很强，IC₅₀在4-15μg／ml之间。结肠癌SW620细胞是七株肿瘤细胞中对化合物的毒性作用最敏感的一株，IC₅₀＜5μg／ml。由于当归酰氧基克拉文酸和巴豆酰氧基克拉文酸在对正常人单个核细胞的体外毒性实验中显示了它们较低的毒性(IC₅₀＞50μg／ml)，所以二者有望成为一类新型抗肿瘤药物的前导化合物。本文为今后进一步利用该植物开发抗肿瘤药提供了科学的数据。更多还原

【Abstract】 Plants are known to possess many different components or secondary metabolites which have various biological activities, including anticancer. Plants have become the invaluable sources of searching for potential anticancer reagents. To exploit new-type anticancer drugs from the abundant toxic plant resources, we collected 41 species of toxic plants, and screened the bioactivities of their petroleum ether, ethyl acetate and methanol extracts by MTT assay in vitro.The preliminary result of MTT assay on the screening for anticancer activities of toxic plants shows that inflorescence of Solidago canadensis contains strong anticancer compounds. Its PE and EtOAc extracts are effective in the suppression of proliferation of the seven different human tumor cell lines, cervical tumour cell Hela, liver tumour cell SMMC 7721, human myelogenous leukaemia K-562, human lung adenocarcinoma SPC-A1, breast cancer Bcap37, MCF-7 and human colon carcinoma SW620 in a dose-dependent pattern. Their IC50 on seven human tumor cell lines are in the range of 15 and 40 μg/ml. Two active diterpenes, 6p-angeloyloxykolavenic acid and 6β-tigloyloxykolavenic acid which can induce the cytotoxic action against cancer cells and initiate anti-proliferation pathway leading to cancer cell death at the concentrations of 7-12 μg/ml, were identified by nuclear magnetic resonance. Though angeloyloxykolavenic acid and tigloyloxykolavenic acid are strong in their anti-tumor activities, their cytotoxicity on peripheral blood monocyte cell is much lesser, IC₅₀> 50 μg/ml. The little cytotoxicity of the two active diterpenes to peripheral blood monocyte cell makes Solidago canadensis L. （tribe Astereae, family Compositae） a potential candidate for anti-tumor medicine.It is first report about the anticancer activities of S. canadensis and its two diterpenes. Our results provide material evidence to develop the potential anticancer medicine from Solidago canadensis L.更多还原