Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica
文献类型：期刊论文
| 作者 | Liang, Xinmiao1,4; Du, Nana1,2; Liu, Yanfang1; Zhang, Xiuli1; Wang, Jixia1; Zhao, Jianqiang2,3; He, Jian1; Zhou, Han1; Mei, Lijuan3 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017-04-07 |
| 卷号 | 7 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep46067 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | TANDEM MASS-SPECTROMETRY ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; TROPANE ALKALOIDS ; GPR35 AGONISTS ; RAT URINE ; SCOPOLAMINE ; ATROPINE ; METABOLITES ; INHIBIT ; DISEASE |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000398641900001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/169310]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Liang, Xinmiao; Liu, Yanfang |
| 作者单位 | 1.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 |
| 推荐引用方式 GB/T 7714 | Liang, Xinmiao,Du, Nana,Liu, Yanfang,et al. Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Liang, Xinmiao.,Du, Nana.,Liu, Yanfang.,Zhang, Xiuli.,Wang, Jixia.,...&Mei, Lijuan.(2017).Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica.SCIENTIFIC REPORTS,7. |
| MLA | Liang, Xinmiao,et al."Discovery of new muscarinic acetylcholine receptor antagonists from Scopolia tangutica".SCIENTIFIC REPORTS 7(2017). |
入库方式： OAI收割
来源：大连化学物理研究所
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