【作者】 赵庆春； 郭涛； 赵明宏； 华威； 付艳辉； 张琳； 吴立军； 王乃利； 姚新生；

【Author】 Qingchun Zhao,a,* Tao Guo,a Minghong Zhao,a Wei Hua,b Yanhui Fu,b Lin Zhang,b Lijun Wu,b Naili Wang,c and Xinsheng Yaoc aThe General Hospital of Shenyang Military Command, Wenhua-Road 83, Shenyang 110016, China bShenyang Pharmaceutical University, Wenhua-Road 103, Shenyang 110015, China, c Traditional Chinese Medicine and Natural Products Research Center, Shenzhen 518055, China

【机构】 沈阳军区总医院药剂科； 沈阳药科大学； 深圳中药和天然药物研究中心；

【摘要】 目的胡蔓藤(又名钩吻)在中国民间被广泛用于抗肿瘤、止痛和增强免疫等,并且曾经被某些国家收入药典用于治疗感冒等疾病。但是由于其毒性剧烈,现行版的药典中已经不再收载,不过其特有的抗癌、止痛、增强免疫活性,又吸引人们不断进行研究以发现高效的活性先导化合物,本文的目的是针对胡蔓藤抗癌活性进行化学研究。方法药材粉碎后用3%NaOH碱化后,晾干,氯仿浸泡,回收氯仿得浸膏。加酸溶解,氯仿萃取,取水层,碱化后,再用氯仿萃取,得到钩吻总生物碱。然后经硅胶减压柱层析、ODS柱层析及制备型HPLC层析分离纯化。经测定理化性质和光谱学数据进行单体化合物的结构鉴定。结果通过A-375细胞毒活性追踪的提取分离过程,分别得到10个生物碱类成分和1个香豆素类、1个邻苯二甲酸酯类和3个萜类化合物成分,分别是gelsequinoline A(1),gelsenine(2),gelseponicine(3),gelseponidine(4),methoxyhum antenine(5),koumine(6),gelsemine(7),gelsevirine(8),humantenine(9),humantenmine(10),滨蒿内酯(11)、二(2-乙基-己基)邻苯二甲酸酯(12)、27–p-(Z)-coumaroyloxy ursolic acid(13)、27–p-(E)-coumaroyloxy ursolic acid(14)、uncarinic acid E(15)。结论其中化合物1～5为新化合物,化合物6～10为已知化合物,化合物11～15为首次从该属植物中分离得到。抗肿瘤活性测试结果表明,生物碱成分的抗肿瘤活性较弱,而化合物12,13,14具有明显的抗肿瘤活性。更多还原

【Abstract】 OBJECTIVE Gelsemium elegans Benth., of which Gou-wen is the Chinese name, has been used as a folk medicine for its antitumor and analgesic properties. It was at one time recognized in several pharmacopoeias and found use in the treatment of influenza.1 For toxicity reasons, it is no longer included in the current pharmacopoeias and for activity reasons, it is interesting to find various lead activity compounds. In this report, we wish to investigate the cytotoxic constituents from the whole plant of Gelsemium elegans Benth. METHODS The plant was alkalified with 3% NaOH, dried at room temperature, then was extracted with CHCl3. The chloroform extract was dissolved in the acid water, partitioned with CHCl3, then the water layer was alkalified with saturate NaOH, extracted with CHCl3 again to obtain the alkaloids of Gelsemium elegans. The alkaloids were further subjected on the silica-gel column, and pre-HPLC chromatography. The physical-chemical data and 1D-NMR, 2D-NMR of the components were determined. RESULTS Ten alkaloids, a coumarin, a phthalate and three terpene were isolated from the whole plants of Gelsemium elegans by the way of a cytotoxicity-guided fractionation procedure against A-375 cell and the structure were determined as gelsequinoline A (1), gelsenine (2), gelseponicine (3), gelseponidine (4), methoxyhumantenine (5), koumine (6), gelsemine (7), gelsevirine (8), humantenine (9) and humantenmine (10), scoparon(11), Di (2-ethylhexyl) phthalate (12), 27–p-(Z)-coumaroyloxy ursolic acid(13), 27–p-(E)-coumaroyloxy ursloic acid(14), Uncarinic acid E(15). CONCLUSION Compound 1～5 are novel compounds. Compound 6～10 are known compounds. Compound 11～15 are isolated from the genus for the first time. The compounds were evaluated for cytotoxicity against A375 cell lines and alkaloids exhibited marginal to moderated cytotoxicity. Compound 12～14 showed a strong bioactivity on A375 cell lines.更多还原