DICP OpenIR
Discovery of novel antagonists on (2)-adrenoceptor from natural products using a label-free cell phenotypic assay
Zhang, Pengyu1; Wang, Jixia2,3; Zhao, Ying1; Zhang, Xiuli2,4; Qu, Lala2; Wang, Chaoran2,3; Feng, Jiatao2,3; Wang, Anhui5,6; Zhou, Weijia2; Liu, Yanfang2,3; Hou, Tao2; Zhou, Han2; Wang, Zhiwei3; Liang, Xinmiao2,3,4
Corresponding AuthorZhao, Ying(zhaoying20001105@126.com) ; Zhang, Xiuli(zhangxiuli@dicp.ac.cn)
Keywordbeta(2)-Adrenoceptor Antagonist Natural product Label-free cell phenotypic assay
Source PublicationNAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
2018-12-01
ISSN0028-1298
DOI10.1007/s00210-018-1555-8
Volume391Issue:12Pages:1411-1420
WOS SubjectPharmacology & Pharmacy
WOS Research AreaPharmacology & Pharmacy
WOS KeywordBETA-ADRENOCEPTOR ANTAGONISTS ; PROTEIN-COUPLED RECEPTORS ; OPTICAL BIOSENSOR ; BLOOD-PRESSURE ; HEART-FAILURE ; LIVING CELLS ; HYPERTENSION ; PHARMACOLOGY
AbstractLabel-free cell phenotypic assays were performed to establish a (2)-adrenoceptor ((2)-AR) target model in A431 cells and a (1)-AR target model in transfected HEK293-(1) cells, using known (2)-AR and (1)-AR agonists and antagonists. A list of natural compounds was screened on the target models, among which seven new compounds were found to be antagonistically active against (2)-AR. After receptor specificity evaluations on hydroxyl carboxylic acid receptor-2 (-2), histamine receptor (H1R), and (1)-adrenoceptor ((1)-AR), six out of the seven compounds, including nuciferine, epiberberine, harmaline, harmine, palmatine, and columbamine, exhibited specific antagonistic activity against (2)-AR. Epiberberine and palmatine showed the strongest antagonistic activities against (2)-AR with IC50 values of 2.3 +/- 0.2M and 2.6 +/- 0.3M, respectively. Docking palmatine to the crystal structure of human (2)-AR (PDB 5X7D) suggested that the ligand forms a hydrogen bond with N312 and hydrophobic interaction with several amino acid residues in the binding pocket, such as D113 and V114. The kinetic binding profile of palmatine was further investigated using co-stimulation assays. Results suggested that palmatine was a competitive antagonist for (2)-AR. The six novel (2)-AR antagonists provide a promising chemical starting point for identification and optimization of drugs used for treating hypertension, glaucoma, and infantile hemangiomas. This study also lays the foundation for the in-depth investigation of biochemical mechanisms and pharmacological properties of natural compounds.
Language英语
WOS IDWOS:000448849700010
PublisherSPRINGER
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166753
Collection中国科学院大连化学物理研究所
Corresponding AuthorZhao, Ying; Zhang, Xiuli
Affiliation1.Dalian Med Univ, Liaoning Prov Core Lab Med Mol Biol, Dalian 116044, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
3.DICP CMC Innovat Inst Med, Taizhou 225300, Peoples R China
4.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China
5.Dalian Univ Technol, Sch Chem, State Key Lab Fine Chem, Dalian 116023, Peoples R China
6.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Peoples R China
Recommended Citation
GB/T 7714
Zhang, Pengyu,Wang, Jixia,Zhao, Ying,et al. Discovery of novel antagonists on (2)-adrenoceptor from natural products using a label-free cell phenotypic assay[J]. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY,2018,391(12):1411-1420.
APA Zhang, Pengyu.,Wang, Jixia.,Zhao, Ying.,Zhang, Xiuli.,Qu, Lala.,...&Liang, Xinmiao.(2018).Discovery of novel antagonists on (2)-adrenoceptor from natural products using a label-free cell phenotypic assay.NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY,391(12),1411-1420.
MLA Zhang, Pengyu,et al."Discovery of novel antagonists on (2)-adrenoceptor from natural products using a label-free cell phenotypic assay".NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 391.12(2018):1411-1420.
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