Catecholic Flavonoids Acting as Telomerase Inhibitors
In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3‘,4‘-tetrahydroxyflavone 1 as a...
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| Veröffentlicht in: | Journal of medicinal chemistry 2004-12, Vol.47 (26), p.6466-6475 |
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| container_end_page | 6475 |
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| container_issue | 26 |
| container_start_page | 6466 |
| container_title | Journal of medicinal chemistry |
| container_volume | 47 |
| creator | Menichincheri, Maria Ballinari, Dario Bargiotti, Alberto Bonomini, Luisella Ceccarelli, Walter D'Alessio, Roberto Fretta, Antonella Moll, Juergen Polucci, Paolo Soncini, Chiara Tibolla, Marcellino Trosset, Jean-Yves Vanotti, Ermes |
| description | In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3‘,4‘-tetrahydroxyflavone 1 as a new telomerase inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 μM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described. |
| doi_str_mv | 10.1021/jm040810b |
| format | Article |
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Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3‘,4‘-tetrahydroxyflavone 1 as a new telomerase inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 μM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm040810b</identifier><identifier>PMID: 15588081</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Biological and medical sciences ; Catechols - chemical synthesis ; Catechols - chemistry ; Flavones - chemical synthesis ; Flavones - chemistry ; General aspects ; Humans ; Medical sciences ; Pharmacology. Drug treatments ; Structure-Activity Relationship ; Telomerase - antagonists & inhibitors ; Telomerase - chemistry</subject><ispartof>Journal of medicinal chemistry, 2004-12, Vol.47 (26), p.6466-6475</ispartof><rights>Copyright © 2004 American Chemical Society</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a447t-4b14957507dbeda66bc00fbe33a74ad3e8c6274c222cb4d3220d9672df63b75c3</citedby><cites>FETCH-LOGICAL-a447t-4b14957507dbeda66bc00fbe33a74ad3e8c6274c222cb4d3220d9672df63b75c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm040810b$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm040810b$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16362036$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15588081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Menichincheri, Maria</creatorcontrib><creatorcontrib>Ballinari, Dario</creatorcontrib><creatorcontrib>Bargiotti, Alberto</creatorcontrib><creatorcontrib>Bonomini, Luisella</creatorcontrib><creatorcontrib>Ceccarelli, Walter</creatorcontrib><creatorcontrib>D'Alessio, Roberto</creatorcontrib><creatorcontrib>Fretta, Antonella</creatorcontrib><creatorcontrib>Moll, Juergen</creatorcontrib><creatorcontrib>Polucci, Paolo</creatorcontrib><creatorcontrib>Soncini, Chiara</creatorcontrib><creatorcontrib>Tibolla, Marcellino</creatorcontrib><creatorcontrib>Trosset, Jean-Yves</creatorcontrib><creatorcontrib>Vanotti, Ermes</creatorcontrib><title>Catecholic Flavonoids Acting as Telomerase Inhibitors</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>In recent years telomerase has been identified as a new promising target in oncology and consequently new telomerase inhibitors have been intensely explored as anticancer agents. Focused screening of several polyhydroxylated flavonoids has allowed us to identify 7,8,3‘,4‘-tetrahydroxyflavone 1 as a new telomerase inhibitor with an interesting in vitro activity in a Flash-Plate assay (IC50 = 0.2 μM) that has been confirmed in the classical TRAP assay. Starting from this compound, we developed a medicinal chemistry program to optimize our lead, and in particular to replace one of the two catechols with potential bioisosteres. From this study, new structural analogues characterized by submicromolar potencies have been obtained. Their synthesis and biological activity are described.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Biological and medical sciences</subject><subject>Catechols - chemical synthesis</subject><subject>Catechols - chemistry</subject><subject>Flavones - chemical synthesis</subject><subject>Flavones - chemistry</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Structure-Activity Relationship</subject><subject>Telomerase - antagonists & inhibitors</subject><subject>Telomerase - chemistry</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0E1PGzEQBmALgUqgPfAHqr1QicPCePy1OUZRQ5EiQCI9W7bXWxx218HeVPDv2SoRufQ0h3nm1egl5ILCNQWkN-sOOFQU7BGZUIFQ8gr4MZkAIJYokZ2Ss5zXAMAosi_klApRVePFhIi5Gbx7jm1wxaI1f2MfQ52LmRtC_6cwuVj5NnY-meyLu_452DDElL-Sk8a02X_bz3Pye_FzNf9VLh9u7-azZWk4V0PJLeVToQSo2vraSGkdQGM9Y0ZxUzNfOYmKO0R0ltcMEeqpVFg3klklHDsnP3a5mxRftz4PugvZ-bY1vY_brKWiilOGI7zaQZdizsk3epNCZ9K7pqD_daQ_Oxrt933o1na-Psh9KSO43AOTnWmbZHoX8sFJJhGYHF25cyEP_u1zb9LL-BhTQq8enzSySop7dqsXh1zjsl7HberH7v7z4AfGI4e7</recordid><startdate>20041216</startdate><enddate>20041216</enddate><creator>Menichincheri, Maria</creator><creator>Ballinari, Dario</creator><creator>Bargiotti, Alberto</creator><creator>Bonomini, Luisella</creator><creator>Ceccarelli, Walter</creator><creator>D'Alessio, Roberto</creator><creator>Fretta, Antonella</creator><creator>Moll, Juergen</creator><creator>Polucci, Paolo</creator><creator>Soncini, Chiara</creator><creator>Tibolla, Marcellino</creator><creator>Trosset, Jean-Yves</creator><creator>Vanotti, Ermes</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><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></search><sort><creationdate>20041216</creationdate><title>Catecholic Flavonoids Acting as Telomerase Inhibitors</title><author>Menichincheri, Maria ; Ballinari, Dario ; Bargiotti, Alberto ; Bonomini, Luisella ; Ceccarelli, Walter ; D'Alessio, Roberto ; Fretta, Antonella ; Moll, Juergen ; Polucci, Paolo ; Soncini, Chiara ; Tibolla, Marcellino ; Trosset, Jean-Yves ; Vanotti, Ermes</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a447t-4b14957507dbeda66bc00fbe33a74ad3e8c6274c222cb4d3220d9672df63b75c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Biological and medical sciences</topic><topic>Catechols - chemical synthesis</topic><topic>Catechols - chemistry</topic><topic>Flavones - chemical synthesis</topic><topic>Flavones - chemistry</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure-Activity Relationship</topic><topic>Telomerase - antagonists & inhibitors</topic><topic>Telomerase - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Menichincheri, Maria</creatorcontrib><creatorcontrib>Ballinari, Dario</creatorcontrib><creatorcontrib>Bargiotti, Alberto</creatorcontrib><creatorcontrib>Bonomini, Luisella</creatorcontrib><creatorcontrib>Ceccarelli, Walter</creatorcontrib><creatorcontrib>D'Alessio, Roberto</creatorcontrib><creatorcontrib>Fretta, Antonella</creatorcontrib><creatorcontrib>Moll, Juergen</creatorcontrib><creatorcontrib>Polucci, Paolo</creatorcontrib><creatorcontrib>Soncini, Chiara</creatorcontrib><creatorcontrib>Tibolla, Marcellino</creatorcontrib><creatorcontrib>Trosset, Jean-Yves</creatorcontrib><creatorcontrib>Vanotti, Ermes</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Menichincheri, Maria</au><au>Ballinari, Dario</au><au>Bargiotti, Alberto</au><au>Bonomini, Luisella</au><au>Ceccarelli, Walter</au><au>D'Alessio, Roberto</au><au>Fretta, Antonella</au><au>Moll, Juergen</au><au>Polucci, Paolo</au><au>Soncini, Chiara</au><au>Tibolla, Marcellino</au><au>Trosset, Jean-Yves</au><au>Vanotti, Ermes</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Catecholic Flavonoids Acting as Telomerase Inhibitors</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. 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| subjects | Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Biological and medical sciences Catechols - chemical synthesis Catechols - chemistry Flavones - chemical synthesis Flavones - chemistry General aspects Humans Medical sciences Pharmacology. Drug treatments Structure-Activity Relationship Telomerase - antagonists & inhibitors Telomerase - chemistry |
| title | Catecholic Flavonoids Acting as Telomerase Inhibitors |
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