Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment
A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced whe...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2014-01, Vol.22 (2), p.756-761 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 761 |
|---|---|
| container_issue | 2 |
| container_start_page | 756 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 22 |
| creator | Nortcliffe, Andrew Ekstrom, Alexander G. Black, James R. Ross, James A. Habib, Fouad K. Botting, Nigel P. O’Hagan, David |
| description | A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac–NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release. |
| doi_str_mv | 10.1016/j.bmc.2013.12.014 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1516747375</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089613010080</els_id><sourcerecordid>1516747375</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-73ed6d822e54ef21099d12371660cfa62b1b45488de4d2baa50aef2c24743ee73</originalsourceid><addsrcrecordid>eNp9kMFu1DAURS1ERaeFD2CDvGST4Gc7TiJWqGopUiUWhbXl2C_Fo8QebKeif1-PprBk5cU79-r6EPIeWAsM1Kd9O6225QxEC7xlIF-RHUglGyFGeE12bFRDw4ZRnZOLnPeMMS5HeEPOuRRDP6huRw73T6H8wuwzNcHRycclPnhrFoqPZtlM8THQONPgS_KWxj_eYeNiqIfwUCOm4hvmI5K3xQdnLJ1joocUczEFqTXBYqIloSkrhvKWnM1myfju5b0kP2-uf1zdNnffv367-nLXWDGo0vQCnXID59hJnDmwcXTARQ9KMTsbxSeYZCeHwaF0fDKmY6ZylsteCsReXJKPp9665HddWPTqs8VlMQHjljV0oHrZi76rKJxQW0fnhLM-JL-a9KSB6aNovddVtD6K1sB1FV0zH17qt2lF9y_x12wFPp8ArJ989Jh0th6rC-cT2qJd9P-pfwb34ZA2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1516747375</pqid></control><display><type>article</type><title>Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Nortcliffe, Andrew ; Ekstrom, Alexander G. ; Black, James R. ; Ross, James A. ; Habib, Fouad K. ; Botting, Nigel P. ; O’Hagan, David</creator><creatorcontrib>Nortcliffe, Andrew ; Ekstrom, Alexander G. ; Black, James R. ; Ross, James A. ; Habib, Fouad K. ; Botting, Nigel P. ; O’Hagan, David</creatorcontrib><description>A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac–NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2013.12.014</identifier><identifier>PMID: 24387865</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Furoxan ; Humans ; Male ; Molecular Structure ; Nitric oxide ; Nitric Oxide - chemistry ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - pathology ; Structure-Activity Relationship ; Sulindac - chemical synthesis ; Sulindac - chemistry ; Sulindac - pharmacology ; Sulindac analogues ; Sydnonimine</subject><ispartof>Bioorganic & medicinal chemistry, 2014-01, Vol.22 (2), p.756-761</ispartof><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-73ed6d822e54ef21099d12371660cfa62b1b45488de4d2baa50aef2c24743ee73</citedby><cites>FETCH-LOGICAL-c386t-73ed6d822e54ef21099d12371660cfa62b1b45488de4d2baa50aef2c24743ee73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089613010080$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24387865$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nortcliffe, Andrew</creatorcontrib><creatorcontrib>Ekstrom, Alexander G.</creatorcontrib><creatorcontrib>Black, James R.</creatorcontrib><creatorcontrib>Ross, James A.</creatorcontrib><creatorcontrib>Habib, Fouad K.</creatorcontrib><creatorcontrib>Botting, Nigel P.</creatorcontrib><creatorcontrib>O’Hagan, David</creatorcontrib><title>Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac–NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Furoxan</subject><subject>Humans</subject><subject>Male</subject><subject>Molecular Structure</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - chemistry</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Structure-Activity Relationship</subject><subject>Sulindac - chemical synthesis</subject><subject>Sulindac - chemistry</subject><subject>Sulindac - pharmacology</subject><subject>Sulindac analogues</subject><subject>Sydnonimine</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>eNp9kMFu1DAURS1ERaeFD2CDvGST4Gc7TiJWqGopUiUWhbXl2C_Fo8QebKeif1-PprBk5cU79-r6EPIeWAsM1Kd9O6225QxEC7xlIF-RHUglGyFGeE12bFRDw4ZRnZOLnPeMMS5HeEPOuRRDP6huRw73T6H8wuwzNcHRycclPnhrFoqPZtlM8THQONPgS_KWxj_eYeNiqIfwUCOm4hvmI5K3xQdnLJ1joocUczEFqTXBYqIloSkrhvKWnM1myfju5b0kP2-uf1zdNnffv367-nLXWDGo0vQCnXID59hJnDmwcXTARQ9KMTsbxSeYZCeHwaF0fDKmY6ZylsteCsReXJKPp9665HddWPTqs8VlMQHjljV0oHrZi76rKJxQW0fnhLM-JL-a9KSB6aNovddVtD6K1sB1FV0zH17qt2lF9y_x12wFPp8ArJ989Jh0th6rC-cT2qJd9P-pfwb34ZA2</recordid><startdate>20140115</startdate><enddate>20140115</enddate><creator>Nortcliffe, Andrew</creator><creator>Ekstrom, Alexander G.</creator><creator>Black, James R.</creator><creator>Ross, James A.</creator><creator>Habib, Fouad K.</creator><creator>Botting, Nigel P.</creator><creator>O’Hagan, David</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20140115</creationdate><title>Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment</title><author>Nortcliffe, Andrew ; Ekstrom, Alexander G. ; Black, James R. ; Ross, James A. ; Habib, Fouad K. ; Botting, Nigel P. ; O’Hagan, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-73ed6d822e54ef21099d12371660cfa62b1b45488de4d2baa50aef2c24743ee73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Furoxan</topic><topic>Humans</topic><topic>Male</topic><topic>Molecular Structure</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - chemistry</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Structure-Activity Relationship</topic><topic>Sulindac - chemical synthesis</topic><topic>Sulindac - chemistry</topic><topic>Sulindac - pharmacology</topic><topic>Sulindac analogues</topic><topic>Sydnonimine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nortcliffe, Andrew</creatorcontrib><creatorcontrib>Ekstrom, Alexander G.</creatorcontrib><creatorcontrib>Black, James R.</creatorcontrib><creatorcontrib>Ross, James A.</creatorcontrib><creatorcontrib>Habib, Fouad K.</creatorcontrib><creatorcontrib>Botting, Nigel P.</creatorcontrib><creatorcontrib>O’Hagan, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Nortcliffe, Andrew</au><au>Ekstrom, Alexander G.</au><au>Black, James R.</au><au>Ross, James A.</au><au>Habib, Fouad K.</au><au>Botting, Nigel P.</au><au>O’Hagan, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2014-01-15</date><risdate>2014</risdate><volume>22</volume><issue>2</issue><spage>756</spage><epage>761</epage><pages>756-761</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac–NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24387865</pmid><doi>10.1016/j.bmc.2013.12.014</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2014-01, Vol.22 (2), p.756-761 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1516747375 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Furoxan Humans Male Molecular Structure Nitric oxide Nitric Oxide - chemistry Prostate cancer Prostatic Neoplasms - drug therapy Prostatic Neoplasms - pathology Structure-Activity Relationship Sulindac - chemical synthesis Sulindac - chemistry Sulindac - pharmacology Sulindac analogues Sydnonimine |
| title | Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T20%3A53%3A19IST&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=Synthesis%20and%20biological%20evaluation%20of%20nitric%20oxide-donating%20analogues%20of%20sulindac%20for%20prostate%20cancer%20treatment&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Nortcliffe,%20Andrew&rft.date=2014-01-15&rft.volume=22&rft.issue=2&rft.spage=756&rft.epage=761&rft.pages=756-761&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2013.12.014&rft_dat=%3Cproquest_cross%3E1516747375%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=1516747375&rft_id=info:pmid/24387865&rft_els_id=S0968089613010080&rfr_iscdi=true |