几种艾纳香属植物中佛司可林类二萜化合物的靶向分离及环磷腺苷酶激活活性研究

项目名称： 几种艾纳香属植物中佛司可林类二萜化合物的靶向分离及环磷腺苷酶激活活性研究

项目编号： No.81460534

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宋志军

作者单位： 广西壮族自治区药用植物园

项目金额： 43万元

中文摘要： 佛司可林二萜化合物因具有腺苷酸环化酶激活活性而成为研究热点。但是该类化合物在植物中十分罕见。我们首次发现艾纳香属植物山风中含有大量具有佛司可林骨架的二萜化合物。活性筛选和文献调查表明同属植物节节红、见霜黄也可能含有此类成分。我们拟在前期已建UPLC-QTOF-ESIMS数据库的指导下，结合活性追踪，选择山风、节节红、见霜黄等4-5种艾纳香属植物，经柱层析及制备HPLC法等，靶向分离纯化这类目标化合物单体，并运用NMR等现代波谱技术结合CD及单晶衍射等对其结构加以鉴定。然后通过结构修饰、改造，得到这类化合物的系列衍生物，并经竞争性蛋白结合分析法，以腺苷酸环化酶(Ac)活性为指标，考察各化合物对环磷腺苷酶激活活性，探讨这类化合物的构效关系，为创新药物的研发提供先导结构。该研究将为佛司可林类活性物质的大量获取提供新的植物资源，同时也为阐明山风等药用植物的活性物质基础提供依据。

中文关键词： 天然活性成分；中草药；二萜类化合物；环磷腺苷酶激活；构效关系

英文摘要： Forskolin(FSK), a diterpenoid rarely in plants, was highlighted for its adenylate cyclase activation activity. For the first time,we find that FSK type diterpenoids are abundant in Blumea aromatic, which is a Chinese herb medicines. The literature survey suggests that Blumea fistulosa, a herb belong to the Genous Blumea also have forskolin type compounds. Under the regulation and the guidance of our UPLC-QTOF-ESIMS library database, in combination with active tracking method, target compounds of Forskolin type deterpenoids would be isolated from blumea plants, such as B. aromatic, B.fistulosa and so on by means of solvent extraction, column chromatography and preparative HPLC etc. The structures of the isolated compounds will be elucidated on the bases of the modern spectral methods,such as NMR etc, and combination with CD and X-ray single crystal diffraction technology.Followed,a series derivatives of Forsklin will be obtained by structure modification or semisynthesis. The screening of Adenosine cyclophosphate activation of enzyme activity of these compounds will be performed through a competitive protein binding assay with adenylate cyclase (Ac) activity as an index to evaluate structure-activity relationships. This study will provide leading compounds for innovative drug discovery. On the other hand, this project will provide new Chinese medicinal herb sources for FSK type diterpenoids.Third,this study would provide compounds database for pharmacological efficacy mechanism study for B.aromatic,as well as those related medicinal herbs of this genus.

英文关键词： bioactive compounds;TCM;diterpenoids;Adenosine cyclophosphate enzyme;bio-structure relationships