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Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica
Du, Nana1,2; Liu, Yanfang1; Zhang, Xiuli1; Wang, Jixia1; Zhao, Jianqiang2,3; He, Jian1; Zhou, Han1; Mei, Lijuan3; Liang, Xinmiao1,4
2017-04-07
Source PublicationSCIENTIFIC REPORTS
Volume7
SubtypeArticle
AbstractScopolia 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.
WOS HeadingsScience & Technology
DOI10.1038/srep46067
WOS KeywordTANDEM MASS-SPECTROMETRY ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; TROPANE ALKALOIDS ; GPR35 AGONISTS ; RAT URINE ; SCOPOLAMINE ; ATROPINE ; METABOLITES ; INHIBIT ; DISEASE
Indexed BySCI
Language英语
Funding OrganizationState Key Program of National Natural Science of China(U1508221) ; NSFC(NSFC 21305138 ; Creative Research Group Project, National Natural Science Funds of China(21321064) ; 81473436 ; 21405155)
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000398641900001
Citation statistics
Document Type期刊论文
Identifierhttp://210.75.249.4/handle/363003/6824
Collection中国科学院西北高原生物研究所
Affiliation1.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Tibetan Med Res, Xining 810008, Peoples R China
4.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China
Recommended Citation
GB/T 7714
Du, Nana,Liu, Yanfang,Zhang, Xiuli,et al. Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica[J]. SCIENTIFIC REPORTS,2017,7.
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,7.
MLA Du, Nana,et al."Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica".SCIENTIFIC REPORTS 7(2017).
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