【作者】 牟宜坤；

【导师】 李玛琳； 雷秀玲；

【作者基本信息】 昆明医学院 ， 药理学， 2003， 硕士

【摘要】 目的：天然酚类、萜类和皂甙类化合物是几种十分重要的天然产物类型，广泛存在于自然界，资源十分丰富，作为潜在的活性物质来源具有较高的研究价值。本次研究的样品是从天然产物中分离得到的73种酚类、萜类、甾体皂甙类化合物或富集了上述化合物的粗提物，本文对受试样品的体外抗肿瘤活性及免疫毒性进行了研究，并对其中二萜类化合物进行了构效关系的分析。方法：采用改良MTT法或SRB法用7-8个人肿瘤细胞株测试了73种天然产物的体外抗肿瘤活性，并用改良MTT法用小鼠脾脏淋巴细胞测试了9种天然产物的免疫毒性。结果：（1）41种样品中有19种化合物对K562细胞和Bcap-37细胞增殖IC₅₀均小于30μg／ml；其中化合物Ir-20对7株人肿瘤细胞增殖的IC₅₀均小于1μg／ml，对小鼠T、B淋巴细胞增殖的IC₅₀也小于10μg／ml；化合物Ir-18、Xe-B对7株人肿瘤细胞增殖的IC₅₀均小于10μg／ml，化合物Ir-13、Il-2、Xe-A、Ma-B对部分人肿瘤细胞增殖的IC₅₀小于10μg／ml，其中Ir-13在浓度为100μg／ml时对小鼠T淋巴细胞增殖抑制率小于31％。（2）32种天然产物中，甾体皂甙Y20对7株肿瘤细胞增殖的IC₅₀均小于10μg／ml，粗提物YP43对7株肿瘤细胞增殖的IC₅₀小于30μg／ml，粗提物YP46、YP47、YP48、YP41、YP49对5～6个人肿瘤细胞株增殖的IC₅₀小于30μg／ml。结论：（1）化合物Ir-20对所测的7株人肿瘤细胞均有显著的细胞毒活性，但对免疫细胞毒性也较强；化合物Ir-18、Xe-B、Ir-13、Il-2、Xe-A、Ma-B对5～6株人肿瘤细胞具有较强的细胞毒活性，上述7种化合物值得进一步深入研究。分析其构效关系表明分子结构中的α-亚甲基环戊酮为该类化合物的细胞毒活性中心。（2）甾体皂甙Y20和甾体皂甙部位粗提物YP43有较强的抗肿瘤活性；甾体皂甙YP46、YP47、YP48、YP41、YP49也有一定的抗肿瘤活性，以上共7种天然产物具有进一步研究的价值。更多还原

【Abstract】 OBJECTIVE: The antitumor activities of 73 natural products (crude extracts or compounds including phenols, terpenes glucosides et.al) isolated from plants of YUNNAN were tested using human tumor cell lines. The cytotoxicities on lymphocytes of 9 products were further assayed using mouse spleen lymphocytes and preliminary analysis of the structure-activity relationship of diterphenoids. METHODS: The cytotoxicity of 73 natural products in 9 human tumor cell lines was measured by modified MTT or SRB assay. RESULTS: (1) The IC50 of 19 compounds out of 41 is less than 30 μ g/ml in K562 and Bcap-37 cell lines. The IC50 of Ir-20 is less than 1 μ g/ml in 7 human tumor cell lines. The IC50 of Ir-18, Xe-B are less than 10 μ g/ml in 7 human rumor cell lines. The IC50 of Ir-13, 11-2, Xe-A, Ma-B is less than 10μg/ml in several human tumor cell lines. The IC50 of the above 6 compounds is less than that of cisplatin in several human tumor cell lines tested. (2) 6 crude extract and 1 compounds are found to have strong cytotoxicity to human tumor cell out of 32 natural products. The IC50 of Y20 is less than 10μg/ml in 7 tumor cells, The IC50 of a crude extract YP43 in 7 tumor cell lines is less than 30μg/ml .CONCLUSION:(1 )Diterpenoids Ir-20, Ir-18. Xe-B show significant cytotoxicity in all human tumor cell lines tested. Diterpenoids Ir-13, 11-2, Xe-B, Ma-B show significant cytotoxicity in 5-6human tumor cell lines. Analysis of the structural-activity relationship reveals that the a-methylene cyclopentanone moity is responsible for the antitumor activity of the diterpenoids tested. (2) Compound Y20 and crude exact YP43 presents strong cytotoxicity for 7 human tumor cell lines, crude extracts YP46, YP47, YP48, YP49, YP41 show significant cytotoxicity in several human tumor cell lines.更多还原