Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein
The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a seri...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2012-03, Vol.55 (5), p.2144-2153 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2153 |
|---|---|
| container_issue | 5 |
| container_start_page | 2144 |
| container_title | Journal of medicinal chemistry |
| container_volume | 55 |
| creator | Cheng, Huimin Wan, Junting Lin, Meng-I Liu, Yingxue Lu, Xiaoyun Liu, Jinsong Xu, Yong Chen, Jianxin Tu, Zhengchao Cheng, Yih-Shyun E Ding, Ke |
| description | The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation. |
| doi_str_mv | 10.1021/jm2013503 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_927691626</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>927691626</sourcerecordid><originalsourceid>FETCH-LOGICAL-a236t-fd209c1a8ec7b94b8521f96da564f870f8bb76e96eecacb4a77cb0647880a2753</originalsourceid><addsrcrecordid>eNo90c1u1DAQB3ALgehSOPACyBfEZQ32OHGS4_YDilTBgYVrNHEmwSvHLnay0L4Nb0pQC6eZw0_zH80w9lLJt0qCeneYQCpdSv2IbVQJUhS1LB6zjZQAAgzoE_Ys54OUUivQT9kJgNZQN8WG_b6g7Maw5V9uw_x97fOWY-i5C_ybm1PkZy76ODqLnl8e0S84uxh4HLi6EmoLWy32yeFd9CQKYTF18RdOrid-QckdV32kzDHzT_ST78LshAuDXyjcId_x3UhhznyPaaTZhXHNTMtqF-sp3qQ4kwvP2ZMBfaYXD_WUfX1_uT-_EtefP3w8310LBG1mMfQgG6uwJlt1TdHVJaihMT2WphjqSg5111WGGkNk0XYFVpXtpCmqupYIValP2Zv7uWvuj4Xy3E4uW_IeA8Ultw1UplEGzCpfPcilm6hvb5KbMN22_666gtf3AG1uD3FJYV28VbL9-632_7f0H7-VhP0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>927691626</pqid></control><display><type>article</type><title>Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Cheng, Huimin ; Wan, Junting ; Lin, Meng-I ; Liu, Yingxue ; Lu, Xiaoyun ; Liu, Jinsong ; Xu, Yong ; Chen, Jianxin ; Tu, Zhengchao ; Cheng, Yih-Shyun E ; Ding, Ke</creator><creatorcontrib>Cheng, Huimin ; Wan, Junting ; Lin, Meng-I ; Liu, Yingxue ; Lu, Xiaoyun ; Liu, Jinsong ; Xu, Yong ; Chen, Jianxin ; Tu, Zhengchao ; Cheng, Yih-Shyun E ; Ding, Ke</creatorcontrib><description>The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm2013503</identifier><identifier>PMID: 22332894</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amantadine - pharmacology ; Amides - chemical synthesis ; Amides - chemistry ; Amides - pharmacology ; Animals ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Cell Line ; Dogs ; Drug Design ; Drug Resistance, Viral ; Influenza A virus - drug effects ; Influenza A virus - metabolism ; Influenza A Virus, H1N1 Subtype - drug effects ; Influenza A Virus, H3N2 Subtype - drug effects ; Influenza A Virus, H5N1 Subtype - drug effects ; Models, Molecular ; Nucleoproteins - metabolism ; Oseltamivir - pharmacology ; Piperazines - chemical synthesis ; Piperazines - chemistry ; Piperazines - pharmacology ; Structure-Activity Relationship ; Triazoles - chemical synthesis ; Triazoles - chemistry ; Triazoles - pharmacology ; Viral Core Proteins - metabolism ; Viral Plaque Assay ; Virus Replication - drug effects</subject><ispartof>Journal of medicinal chemistry, 2012-03, Vol.55 (5), p.2144-2153</ispartof><rights>Copyright © 2012 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm2013503$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm2013503$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22332894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Huimin</creatorcontrib><creatorcontrib>Wan, Junting</creatorcontrib><creatorcontrib>Lin, Meng-I</creatorcontrib><creatorcontrib>Liu, Yingxue</creatorcontrib><creatorcontrib>Lu, Xiaoyun</creatorcontrib><creatorcontrib>Liu, Jinsong</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Chen, Jianxin</creatorcontrib><creatorcontrib>Tu, Zhengchao</creatorcontrib><creatorcontrib>Cheng, Yih-Shyun E</creatorcontrib><creatorcontrib>Ding, Ke</creatorcontrib><title>Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.</description><subject>Amantadine - pharmacology</subject><subject>Amides - chemical synthesis</subject><subject>Amides - chemistry</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - pharmacology</subject><subject>Cell Line</subject><subject>Dogs</subject><subject>Drug Design</subject><subject>Drug Resistance, Viral</subject><subject>Influenza A virus - drug effects</subject><subject>Influenza A virus - metabolism</subject><subject>Influenza A Virus, H1N1 Subtype - drug effects</subject><subject>Influenza A Virus, H3N2 Subtype - drug effects</subject><subject>Influenza A Virus, H5N1 Subtype - drug effects</subject><subject>Models, Molecular</subject><subject>Nucleoproteins - metabolism</subject><subject>Oseltamivir - pharmacology</subject><subject>Piperazines - chemical synthesis</subject><subject>Piperazines - chemistry</subject><subject>Piperazines - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Triazoles - chemical synthesis</subject><subject>Triazoles - chemistry</subject><subject>Triazoles - pharmacology</subject><subject>Viral Core Proteins - metabolism</subject><subject>Viral Plaque Assay</subject><subject>Virus Replication - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90c1u1DAQB3ALgehSOPACyBfEZQ32OHGS4_YDilTBgYVrNHEmwSvHLnay0L4Nb0pQC6eZw0_zH80w9lLJt0qCeneYQCpdSv2IbVQJUhS1LB6zjZQAAgzoE_Ys54OUUivQT9kJgNZQN8WG_b6g7Maw5V9uw_x97fOWY-i5C_ybm1PkZy76ODqLnl8e0S84uxh4HLi6EmoLWy32yeFd9CQKYTF18RdOrid-QckdV32kzDHzT_ST78LshAuDXyjcId_x3UhhznyPaaTZhXHNTMtqF-sp3qQ4kwvP2ZMBfaYXD_WUfX1_uT-_EtefP3w8310LBG1mMfQgG6uwJlt1TdHVJaihMT2WphjqSg5111WGGkNk0XYFVpXtpCmqupYIValP2Zv7uWvuj4Xy3E4uW_IeA8Ultw1UplEGzCpfPcilm6hvb5KbMN22_666gtf3AG1uD3FJYV28VbL9-632_7f0H7-VhP0</recordid><startdate>20120308</startdate><enddate>20120308</enddate><creator>Cheng, Huimin</creator><creator>Wan, Junting</creator><creator>Lin, Meng-I</creator><creator>Liu, Yingxue</creator><creator>Lu, Xiaoyun</creator><creator>Liu, Jinsong</creator><creator>Xu, Yong</creator><creator>Chen, Jianxin</creator><creator>Tu, Zhengchao</creator><creator>Cheng, Yih-Shyun E</creator><creator>Ding, Ke</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20120308</creationdate><title>Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein</title><author>Cheng, Huimin ; Wan, Junting ; Lin, Meng-I ; Liu, Yingxue ; Lu, Xiaoyun ; Liu, Jinsong ; Xu, Yong ; Chen, Jianxin ; Tu, Zhengchao ; Cheng, Yih-Shyun E ; Ding, Ke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a236t-fd209c1a8ec7b94b8521f96da564f870f8bb76e96eecacb4a77cb0647880a2753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amantadine - pharmacology</topic><topic>Amides - chemical synthesis</topic><topic>Amides - chemistry</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - pharmacology</topic><topic>Cell Line</topic><topic>Dogs</topic><topic>Drug Design</topic><topic>Drug Resistance, Viral</topic><topic>Influenza A virus - drug effects</topic><topic>Influenza A virus - metabolism</topic><topic>Influenza A Virus, H1N1 Subtype - drug effects</topic><topic>Influenza A Virus, H3N2 Subtype - drug effects</topic><topic>Influenza A Virus, H5N1 Subtype - drug effects</topic><topic>Models, Molecular</topic><topic>Nucleoproteins - metabolism</topic><topic>Oseltamivir - pharmacology</topic><topic>Piperazines - chemical synthesis</topic><topic>Piperazines - chemistry</topic><topic>Piperazines - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Triazoles - chemical synthesis</topic><topic>Triazoles - chemistry</topic><topic>Triazoles - pharmacology</topic><topic>Viral Core Proteins - metabolism</topic><topic>Viral Plaque Assay</topic><topic>Virus Replication - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Huimin</creatorcontrib><creatorcontrib>Wan, Junting</creatorcontrib><creatorcontrib>Lin, Meng-I</creatorcontrib><creatorcontrib>Liu, Yingxue</creatorcontrib><creatorcontrib>Lu, Xiaoyun</creatorcontrib><creatorcontrib>Liu, Jinsong</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Chen, Jianxin</creatorcontrib><creatorcontrib>Tu, Zhengchao</creatorcontrib><creatorcontrib>Cheng, Yih-Shyun E</creatorcontrib><creatorcontrib>Ding, Ke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Huimin</au><au>Wan, Junting</au><au>Lin, Meng-I</au><au>Liu, Yingxue</au><au>Lu, Xiaoyun</au><au>Liu, Jinsong</au><au>Xu, Yong</au><au>Chen, Jianxin</au><au>Tu, Zhengchao</au><au>Cheng, Yih-Shyun E</au><au>Ding, Ke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2012-03-08</date><risdate>2012</risdate><volume>55</volume><issue>5</issue><spage>2144</spage><epage>2153</epage><pages>2144-2153</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC50 values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>22332894</pmid><doi>10.1021/jm2013503</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2012-03, Vol.55 (5), p.2144-2153 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_927691626 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Amantadine - pharmacology Amides - chemical synthesis Amides - chemistry Amides - pharmacology Animals Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Cell Line Dogs Drug Design Drug Resistance, Viral Influenza A virus - drug effects Influenza A virus - metabolism Influenza A Virus, H1N1 Subtype - drug effects Influenza A Virus, H3N2 Subtype - drug effects Influenza A Virus, H5N1 Subtype - drug effects Models, Molecular Nucleoproteins - metabolism Oseltamivir - pharmacology Piperazines - chemical synthesis Piperazines - chemistry Piperazines - pharmacology Structure-Activity Relationship Triazoles - chemical synthesis Triazoles - chemistry Triazoles - pharmacology Viral Core Proteins - metabolism Viral Plaque Assay Virus Replication - drug effects |
| title | Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3-Triazole-4-carboxamide Derivatives as New Anti-influenza A Agents Targeting Virus Nucleoprotein |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T16%3A43%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Design,%20Synthesis,%20and%20in%20Vitro%20Biological%20Evaluation%20of%201H-1,2,3-Triazole-4-carboxamide%20Derivatives%20as%20New%20Anti-influenza%20A%20Agents%20Targeting%20Virus%20Nucleoprotein&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Cheng,%20Huimin&rft.date=2012-03-08&rft.volume=55&rft.issue=5&rft.spage=2144&rft.epage=2153&rft.pages=2144-2153&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/jm2013503&rft_dat=%3Cproquest_pubme%3E927691626%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=927691626&rft_id=info:pmid/22332894&rfr_iscdi=true |