Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica

NWIPB OpenIR

	Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica
	Du, Nana ; Liu, Yanfang ; Zhang, Xiuli ; Wang, Jixia ; Zhao, Jianqiang ; He, Jian ; Zhou, Han ; Mei, Lijuan ; Liang, Xinmiao
	2017-04-07
发表期刊	SCIENTIFIC REPORTS
摘要	Scopolia tangutica (S. tangutica) is a traditional Chinese medicinal plant used for antispasmodics, anesthesia, analgesia and sedation. Its pharmacological activities are mostly associated with the antagonistic activity at muscarinic acetylcholine receptors (mAchRs) of several known alkaloids such as atropine and scopolamine. With our recent identification of four hydroxycinnamic acid amides from S. tangutica, we hypothesized that this plant may contain previously unidentified alkaloids that may also contribute to its in vivo effect. Herein, we used a bioassay-guided multi-dimension separation strategy to discover novel mAchR antagonists from S. tangutica. The core of this approach is to use label-free cell phenotypic assay to first identify active fractions, and then to guide purification of active ligands. Besides four tropanes and six cinnamic acid amides that have been previously isolated from S. tangutica, we recently identified two new tropanes, one new cinnamic acid amide, and nine other compounds. Six tropane compounds purified from S. tangutica for the first time were confirmed to be competitive antagonists of muscarinic receptor 3 (M3), including the two new ones 8 and 12 with IC50 values of 1.97 mu M and 4.47 mu M, respectively. Furthermore, the cinnamic acid amide 17 displayed 15-fold selectivity for M1 over M3 receptors. These findings will be useful in designing lead compounds for mAchRs and elucidating mechanisms of action of S. tangutica.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/58604
专题	中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Du, Nana,Liu, Yanfang,Zhang, Xiuli,et al. Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica[J]. SCIENTIFIC REPORTS,2017.
APA	Du, Nana.,Liu, Yanfang.,Zhang, Xiuli.,Wang, Jixia.,Zhao, Jianqiang.,...&Liang, Xinmiao.(2017).Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica.SCIENTIFIC REPORTS.
MLA	Du, Nana,et al."Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica".SCIENTIFIC REPORTS (2017).