Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor
Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists w...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2014-11, Vol.22 (21), p.6117-6123 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6123 |
|---|---|
| container_issue | 21 |
| container_start_page | 6117 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 22 |
| creator | Ma, Ming-Liang Li, Ming Gou, Jiao-Jiao Ruan, Tian-Yu Jin, Hai-Shan Zhang, Ling-Hong Wu, Liang-Chun Li, Xiao-Yan Hu, Ying-He Wen, Ke Zhao, Zheng |
| description | Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure–activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2′-fluoride group in ring B were essential for this class of compounds to be active against NMU2R. |
| doi_str_mv | 10.1016/j.bmc.2014.08.038 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1635032701</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089614006348</els_id><sourcerecordid>1629958667</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-931000ec11f7fd80a461989bc73ec299d39104bbd63670cee558875498afe353</originalsourceid><addsrcrecordid>eNqNkc1u3CAUhVHUKpmkfYBuKpZdxM7F2BiUVZV_KVI36RphfD1l5IEpMCPN25fRJFlWWXElvnMunEPINwY1AyauVvWwtnUDrK1B1sDlCVmwVrQV54p9IgtQQlYglTgj5ymtAKBpFTslZ03XiEa1bEHyLSa39Jc07X3-U-ZEjR_p4MIcls6amRqb3c7lPQ0TnWazCz64kY4Y3c6UGyyCRBPOeOCQmmXwLuVEpxCpx20Maxydp79pQyNa3OQQv5DPk5kTfn09L8jL_d3LzWP1_Ovh6ebnc2W5FLlSnJUno2Vs6qdRgmkFU1INtudoG6XG8ktoh2EUXPRgEbtOyr5rlTQT8o5fkB9H200Mf7eYsl67ZHGejcewTZoJ3gFvemAfQMu-TgrRF5QdURtDShEnvYlubeJeM9CHWvRKl1r0oRYNUpdaiub7q_12KHG8K956KMD1EcASx85h1Mk69LZEV0LLegzuP_b_AIDLnhM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1629958667</pqid></control><display><type>article</type><title>Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Ma, Ming-Liang ; Li, Ming ; Gou, Jiao-Jiao ; Ruan, Tian-Yu ; Jin, Hai-Shan ; Zhang, Ling-Hong ; Wu, Liang-Chun ; Li, Xiao-Yan ; Hu, Ying-He ; Wen, Ke ; Zhao, Zheng</creator><creatorcontrib>Ma, Ming-Liang ; Li, Ming ; Gou, Jiao-Jiao ; Ruan, Tian-Yu ; Jin, Hai-Shan ; Zhang, Ling-Hong ; Wu, Liang-Chun ; Li, Xiao-Yan ; Hu, Ying-He ; Wen, Ke ; Zhao, Zheng</creatorcontrib><description>Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure–activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2′-fluoride group in ring B were essential for this class of compounds to be active against NMU2R.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2014.08.038</identifier><identifier>PMID: 25262941</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Drug Design ; Flavonoid derivatives ; Flavonoids - chemical synthesis ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Humans ; NMU2R ; Receptors, Neurotransmitter - agonists ; Receptors, Neurotransmitter - metabolism ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2014-11, Vol.22 (21), p.6117-6123</ispartof><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-931000ec11f7fd80a461989bc73ec299d39104bbd63670cee558875498afe353</citedby><cites>FETCH-LOGICAL-c386t-931000ec11f7fd80a461989bc73ec299d39104bbd63670cee558875498afe353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089614006348$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25262941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Ming-Liang</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Gou, Jiao-Jiao</creatorcontrib><creatorcontrib>Ruan, Tian-Yu</creatorcontrib><creatorcontrib>Jin, Hai-Shan</creatorcontrib><creatorcontrib>Zhang, Ling-Hong</creatorcontrib><creatorcontrib>Wu, Liang-Chun</creatorcontrib><creatorcontrib>Li, Xiao-Yan</creatorcontrib><creatorcontrib>Hu, Ying-He</creatorcontrib><creatorcontrib>Wen, Ke</creatorcontrib><creatorcontrib>Zhao, Zheng</creatorcontrib><title>Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure–activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2′-fluoride group in ring B were essential for this class of compounds to be active against NMU2R.</description><subject>Drug Design</subject><subject>Flavonoid derivatives</subject><subject>Flavonoids - chemical synthesis</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Humans</subject><subject>NMU2R</subject><subject>Receptors, Neurotransmitter - agonists</subject><subject>Receptors, Neurotransmitter - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u3CAUhVHUKpmkfYBuKpZdxM7F2BiUVZV_KVI36RphfD1l5IEpMCPN25fRJFlWWXElvnMunEPINwY1AyauVvWwtnUDrK1B1sDlCVmwVrQV54p9IgtQQlYglTgj5ymtAKBpFTslZ03XiEa1bEHyLSa39Jc07X3-U-ZEjR_p4MIcls6amRqb3c7lPQ0TnWazCz64kY4Y3c6UGyyCRBPOeOCQmmXwLuVEpxCpx20Maxydp79pQyNa3OQQv5DPk5kTfn09L8jL_d3LzWP1_Ovh6ebnc2W5FLlSnJUno2Vs6qdRgmkFU1INtudoG6XG8ktoh2EUXPRgEbtOyr5rlTQT8o5fkB9H200Mf7eYsl67ZHGejcewTZoJ3gFvemAfQMu-TgrRF5QdURtDShEnvYlubeJeM9CHWvRKl1r0oRYNUpdaiub7q_12KHG8K956KMD1EcASx85h1Mk69LZEV0LLegzuP_b_AIDLnhM</recordid><startdate>20141101</startdate><enddate>20141101</enddate><creator>Ma, Ming-Liang</creator><creator>Li, Ming</creator><creator>Gou, Jiao-Jiao</creator><creator>Ruan, Tian-Yu</creator><creator>Jin, Hai-Shan</creator><creator>Zhang, Ling-Hong</creator><creator>Wu, Liang-Chun</creator><creator>Li, Xiao-Yan</creator><creator>Hu, Ying-He</creator><creator>Wen, Ke</creator><creator>Zhao, Zheng</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20141101</creationdate><title>Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor</title><author>Ma, Ming-Liang ; Li, Ming ; Gou, Jiao-Jiao ; Ruan, Tian-Yu ; Jin, Hai-Shan ; Zhang, Ling-Hong ; Wu, Liang-Chun ; Li, Xiao-Yan ; Hu, Ying-He ; Wen, Ke ; Zhao, Zheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-931000ec11f7fd80a461989bc73ec299d39104bbd63670cee558875498afe353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Drug Design</topic><topic>Flavonoid derivatives</topic><topic>Flavonoids - chemical synthesis</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Humans</topic><topic>NMU2R</topic><topic>Receptors, Neurotransmitter - agonists</topic><topic>Receptors, Neurotransmitter - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Ming-Liang</creatorcontrib><creatorcontrib>Li, Ming</creatorcontrib><creatorcontrib>Gou, Jiao-Jiao</creatorcontrib><creatorcontrib>Ruan, Tian-Yu</creatorcontrib><creatorcontrib>Jin, Hai-Shan</creatorcontrib><creatorcontrib>Zhang, Ling-Hong</creatorcontrib><creatorcontrib>Wu, Liang-Chun</creatorcontrib><creatorcontrib>Li, Xiao-Yan</creatorcontrib><creatorcontrib>Hu, Ying-He</creatorcontrib><creatorcontrib>Wen, Ke</creatorcontrib><creatorcontrib>Zhao, Zheng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Ming-Liang</au><au>Li, Ming</au><au>Gou, Jiao-Jiao</au><au>Ruan, Tian-Yu</au><au>Jin, Hai-Shan</au><au>Zhang, Ling-Hong</au><au>Wu, Liang-Chun</au><au>Li, Xiao-Yan</au><au>Hu, Ying-He</au><au>Wen, Ke</au><au>Zhao, Zheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>22</volume><issue>21</issue><spage>6117</spage><epage>6123</epage><pages>6117-6123</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure–activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2′-fluoride group in ring B were essential for this class of compounds to be active against NMU2R.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25262941</pmid><doi>10.1016/j.bmc.2014.08.038</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2014-11, Vol.22 (21), p.6117-6123 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1635032701 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Drug Design Flavonoid derivatives Flavonoids - chemical synthesis Flavonoids - chemistry Flavonoids - pharmacology Humans NMU2R Receptors, Neurotransmitter - agonists Receptors, Neurotransmitter - metabolism Structure-Activity Relationship |
| title | Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T22%3A28%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Design,%20synthesis%20and%20biological%20activity%20of%20flavonoid%20derivatives%20as%20selective%20agonists%20for%20neuromedin%20U%202%20receptor&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Ma,%20Ming-Liang&rft.date=2014-11-01&rft.volume=22&rft.issue=21&rft.spage=6117&rft.epage=6123&rft.pages=6117-6123&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2014.08.038&rft_dat=%3Cproquest_cross%3E1629958667%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1629958667&rft_id=info:pmid/25262941&rft_els_id=S0968089614006348&rfr_iscdi=true |