【作者】 田小雁；

【导师】 庾石山； 方唯硕；

【作者基本信息】 中国协和医科大学 ， 药物化学， 2006， 博士

【摘要】 中草药无论在历史上还是在今天都对中华民族的健康乃至繁衍和生存起到了极其重要的作用。中草药发挥生理作用的物质基础是其中的活性成分。为了从中草药中寻找活性化合物，开发新药和阐明中药作用的机理，我们用活性追踪的方法对四种中草药的化学成分和药理活性进行了研究。 对川续断科川续断属植物续断(Dipsacus asper Wall.)的干燥根的95％乙醇提取物，用噻唑蓝显色法(3-[4，5-dimethyl thiazol-2-yl]-2，5-diphenyltetrazolium bromide，MTT)法确定其抗肿瘤活性部位为正丁醇部分，通过活性追踪的方法对正丁醇部分进行了化学成分研究，寻找到了抗肿瘤活性成分—酚酸类化合物，分离和鉴定了两个酚酸类化合物，并测定了其细胞毒活性；在活性追踪的过程中分离得到了三萜及其苷类化合物5个，鉴定了2个；分离得到了环烯醚萜苷类化合物14个，鉴定了13个。从续断中共分得21个化合物，鉴定了17个化合物，包括8个新化合物，其中两个为首次分离和测定的环烯醚萜苷四聚体化合物。 对菊科千里光属植物千里光(Senecio scandens Buch-Ham)干燥全草的95％乙醇提取物，用MTT法确定了其抗肿瘤活性部位并对活性部位的化学成分进行了研究，寻找到了千里光中的主要抗肿瘤活性成分jacaranone ethyl ester和一些微量活性成分。在活性追踪的过程中从千里光的抗肿瘤有效部位分离测定了12个jacaranone类活性化合物，包括8个新化合物；6个黄酮苷类化合物；1个倍半萜；1个木脂素；2个甾体类化合物；1个单糖。测定了jacaranone类化合物的体外细胞毒活性和iacaranone ethyl ester的体内抗肿瘤活性，对jacaranone类化合物的构效关系进行了初步探讨。同时，利用DPPH法对千里光的甲醇部分的抗氧化活性进行了研究，寻找到了具有抗氧化作用的活性成分—酚酸类化合物，分离并鉴定了8个酚酸类化合物和一个腺苷类化合物。从千里光中共分到37个化合物，测定了32个化合物，包括8个新化合物。 对天南星科千年健属植物千年健(Homalomena occulta Schott.)干燥根茎的95％乙醇提取物，石油醚和氯仿萃取部分显示了一定的β-分泌酶抑制活性，用活性追踪的方法对这两个部位进行了化学成分研究，寻找到了4个活性成分-酚酸酯类化合物。同时在活性追踪的过程中，分离和鉴定了倍半萜类化合物9个，包更多还原

【Abstract】 Chinese traditional and herbal medicines have been used for hundreds of years to cure diseases and save people’s life. In order to search for active components from Chinese traditional and berbal medicines, chemical studies have been carried out on four kinds of herbs including Dipsacus asper Wall., Senecio scandens Buch.-Ham, Homalomena occulta Schott, and Rhodobryum roseum Limp.Bioassay-guided fractionations of the n-BuOH soluble part of D. asper led to the isolation of phenolic acid derivatives as the cytotoxic components, as well as two new iridoid glucoside tetramers (dipsanosides A, B), five new iridoid glucoside dimers (dipsanosides C-G), and one new iridoid glucoside (dipsanoside F). In addition, nine known compounds loganin, cantleyoside, triplostoside A, lisianthioside, 6’-O-(3-D-apiofuranosyl sweroside, caffeic acid, 2, 6-dihydroxyl cinnamic acid, oleanic acid, and akebiasaponin D from the roots of Dipsacus asper. Their structures were determined by spectroscopic and chemical methods, including 1D and 2D NMR techniques.Bioassay-guided fractionations of the ethanol extracts of Senecio scandens led to the isolation of eight new jacaranone analogs 2~7,10, and 11, along with four known jacaranone analogs (1, 8, 9, 12). Among them, compounds 2-6 were obtained as tautomeric mixtures of α/β epimer. Their structures were elucidated on the basis of spectral and chemical evidences. The cytotoxic activities of these compounds were tested. Compounds 7, 8, 9, 11 showed potent cytotoxicities and compounds 2-6 exhibited moderate cytotoxicities against five tumor cell lines. Jacaranone ethyl ester (1), a benzoquinone derivative, was the major cytotoxic constituent in this plant with IC50 values at range of 0.5~1.0 μg/mL against various tumor cell lines. Structure-activity relationship (SAR) of these jacaranone analogs (1-8) isolated from S. scandens was also discussed. Moreover, during the process of bioassay-guided fractionation, 11 known compounds of other structural types were also isolated and characterized. The MeOH part of the ethanol extracts of S. scandens also showed更多还原