拐芹倍半萜没药烷吉酮的结构修饰及其对H^+/K^+-ATP酶的抑制作用  

Structure modification and H^+/K^+-ATPase inhibitory activity of sesquiterpene bisabolangelone from Angelica polymorpha Maxim

作　　者：姚媛[1] 谢田鹏 陈雷[1] 黄年玉[1] 汪鋆植[1] 邹坤[1] 

机构地区：[1]三峡大学生物与制药学院天然产物研究与利用湖北省重点实验室,湖北宜昌443002

出　　处：《生物资源》2017年第2期146-152,共7页Biotic Resources

基　　金：国家自然科学基金(21102084);国家留学基金(201508420062);湖北省自然科学基金项目(2014CFB684);三峡大学青年拔尖人才项目

摘　　要：三峡区域药用植物拐芹的根中富含倍半萜类抗溃疡活性成分没药烷吉酮,为可开发和利用的中草药资源。本文对该化合物进行了提取分离、结构修饰和初步的构效关系研究,从拐芹根茎中提取并分离了没药烷吉酮,通过选择性还原、缩合和加成反应制备了四个没药烷吉酮氨基甲酰腙衍生物。用核磁共振波谱、质谱、红外和元素分析等方法确证了其结构,并测试了其体外对H^+/K^+-ATP酶的抑制活性和细胞毒活性。没药烷吉酮还原衍生物2及4-氯苯基取代的氨基甲酰腙衍生物4d较阳性对照药物奥美拉唑具有更好的体外抗溃疡活性(IC50<24μmol/L)。本文探明了没药烷吉酮衍生物的结构对体外H^+/K^+-ATP酶抑制活性的影响,为消化性溃疡的治疗提供了新型倍半萜类候选药物。The antiulcer sesquiterpene bisabolangelone is rich in the roots of Angelica polymorpha Maxim in the Three Gorges area. In order to develop and apply the bioactive ingredient in the natural medical plants, bisabolangelo- ne was isolated and its structure was modified. Four hydrazinecarboxamides were prepared through selective reduc- tion, condensation and additional reaction, and their structures were characterized by nuclear magnetic resonance （NMR）, electrospray ionization mass spectrometry （ESI-MS）, infrared spectroscopy （IR） and elementaI analysis. They were also evaluated preliminarily for their in vitro H＋/K＋ ATPase inhibition activity and cytotoxicities. The antiulcer activities of bisabolangelone derivitives could be obviously improved by selective reduction derivative 2 and 4- chlorophenyl substituted hydrazinecarboxamide 4d （IC50 〈24 /μmol/L）, which were better than commercial ome- prazole. The research indicated that the bioactivity of bisabolangelone derivatives might be enhanced by inducting some special atoms, and these results provided a new sesquiterpene-type reference drug for the treatment of gastric ulcer.

关 键 词：拐芹 倍半萜 没药烷吉酮 结构修饰 H+/K+-ATP酶抑制活性 

分 类 号：O629.9[理学—有机化学]