贯叶金丝桃素衍生物的合成及其抗老年痴呆和抗肿瘤活性分析-药物分析学专业论文.docxVIP

李义敏 李义敏 中山大学硕十：学位论文 论文题目 贳叶金丝桃素衍生物的合成及其抗老年痴呆和抗肿瘤活性研究 专 业 药物分析学 硕十生 李文敏 指导教师 手冬梅副教授 摘 要 贯叶连翘(Hypericumperforatum L)：藤黄科金丝桃属植物，由其提取物生 产的制剂已在欧美诸国临床上广泛用于治疗中、轻度抑郁症。贯叶会丝桃素 (hyperforin，HF)是贯叶连翘及其制剂抗抑郁的重要活性成分之一，但其遇光、 氧极易发生化学氧化降解。最近的研究发现，HF除具有抗抑郁作用外，还具有 抗肿瘤、抗菌、抗病毒与促进学习记忆等药理活性，是目前国际上研究的热点天 然药物之一。 本论文利用从贯叶连翘药材中提取制备的贯叶连翘粗提物，在一定条件下对 HF进行进一步的分离纯化富集，得到富含HF的提取物作为衍生物合成的原料。 采用酰基化、钯碳还原和成盐反应，合成了一系列HF衍生物单体，并运用NMR、 IR、uv等波谱技术对各衍生物进行了结构鉴定。 运用GLC一82肺癌细胞株检测了各HF衍生物对细胞的生长抑制作用，测定 了各个化合物对GLC-82细胞株的IC50，并深入分析了HF乙酸酯对该细胞株的 生长抑制作用的分子机理。 使用大鼠肾上腺嗜铬细胞瘤细胞株PCI2，采用RT-PCR方法检测了HF乙酸 酯从浓度lOOug／ml到6．25ug／ml作用细胞48小时后，对细胞内源BACEl基因转 录产物的变化，表明HF乙酸酯能影响BACEl的转录活性。在药物浓度达到 100ug／ml时，其活性降到最低。该结果提示了HF乙酸酯可能具有抑制A13肽作 用，从而预防或治疗老年性痴呆症。 关键词：HF衍生物：抗肿瘤；抗老年痴呆；8一分泌酶 贳叶台丝桃索衍生物的合成发】e抗老年痴呆和抗肿瘤活件研究Title：Synthesis 贳叶台丝桃索衍生物的合成发】e抗老年痴呆和抗肿瘤活件研究 Title：Synthesis of hyperforin derivates and their activities on anti-AD and anti．tumours Speciality：Medicinal Analysis Name：Li Wenmin Supervisor：Associate Prof．Wang Dongmei＆Associate Prof．ZHONG Ling ABSTRACT Hypericum perforatum L．(HP)is a sort of wilding of Hypericum which belongs to Gutiiferae．Today，HP has been successful in Germany and other European and American countries as the most salable herbal antidepressant．Hyperforins is one of the main active compounds for depression．However,it is quite instable to light， oxygen and heat．Besides antidepression，hyperforin also possesses anti—cancer, antibacterial，and improving performance of learning and memory in animals． Hyperforin is becoming a hot—spot natural drug in natural medical research． The extracts enriched of hypefforin were prepared from Hypericum perforatum L． Th[ough acylation，reduction and salification，a series of HF derivatives were synthesized，and the structures were identified by H—NMR，C—NMR，m，UV spectra． The IC50 of all hyperforin dedvates in GLC一82 were measued in order to darify the mechanism of their inhibition of the cell generation．The apoptosis and cell cycle were also investigated by FCM． PCI2 cell was used as