[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines
Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated...
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| Veröffentlicht in: | Journal of medicinal chemistry 2006-09, Vol.49 (19), p.5769-5776 |
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| container_issue | 19 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 49 |
| creator | Mahboobi, Siavosh Sellmer, Andreas Höcher, Heymo Eichhorn, Emerich Bär, Thomas Schmidt, Mathias Maier, Thomas Stadlwieser, Josef F Beckers, Thomas L |
| description | Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype. |
| doi_str_mv | 10.1021/jm060545p |
| format | Article |
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A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Mahboobi, Siavosh ; Sellmer, Andreas ; Höcher, Heymo ; Eichhorn, Emerich ; Bär, Thomas ; Schmidt, Mathias ; Maier, Thomas ; Stadlwieser, Josef F ; Beckers, Thomas L</creator><creatorcontrib>Mahboobi, Siavosh ; Sellmer, Andreas ; Höcher, Heymo ; Eichhorn, Emerich ; Bär, Thomas ; Schmidt, Mathias ; Maier, Thomas ; Stadlwieser, Josef F ; Beckers, Thomas L</creatorcontrib><description>Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm060545p</identifier><identifier>PMID: 16970401</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Aniline Compounds - chemical synthesis ; Aniline Compounds - chemistry ; Aniline Compounds - pharmacology ; Antineoplastic agents ; Binding Sites ; Biological and medical sciences ; Cell Line, Tumor ; Cell Shape - drug effects ; Cell Survival - drug effects ; Colchicine - metabolism ; Drug Screening Assays, Antitumor ; General aspects ; Humans ; Medical sciences ; Pharmacology. Drug treatments ; Structure-Activity Relationship ; Thiazoles - chemical synthesis ; Thiazoles - chemistry ; Thiazoles - pharmacology ; Tubulin - metabolism ; Tubulin Modulators - chemical synthesis ; Tubulin Modulators - chemistry ; Tubulin Modulators - pharmacology</subject><ispartof>Journal of medicinal chemistry, 2006-09, Vol.49 (19), p.5769-5776</ispartof><rights>Copyright © 2006 American Chemical Society</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a381t-2f865d173fb64bcc7b14c95c5892ec18c8ba034ecabd2e9ffad9c3a07baaf3d33</citedby><cites>FETCH-LOGICAL-a381t-2f865d173fb64bcc7b14c95c5892ec18c8ba034ecabd2e9ffad9c3a07baaf3d33</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/jm060545p$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm060545p$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18119289$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16970401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mahboobi, Siavosh</creatorcontrib><creatorcontrib>Sellmer, Andreas</creatorcontrib><creatorcontrib>Höcher, Heymo</creatorcontrib><creatorcontrib>Eichhorn, Emerich</creatorcontrib><creatorcontrib>Bär, Thomas</creatorcontrib><creatorcontrib>Schmidt, Mathias</creatorcontrib><creatorcontrib>Maier, Thomas</creatorcontrib><creatorcontrib>Stadlwieser, Josef F</creatorcontrib><creatorcontrib>Beckers, Thomas L</creatorcontrib><title>[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.</description><subject>Aniline Compounds - chemical synthesis</subject><subject>Aniline Compounds - chemistry</subject><subject>Aniline Compounds - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Cell Shape - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Colchicine - metabolism</subject><subject>Drug Screening Assays, Antitumor</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Structure-Activity Relationship</subject><subject>Thiazoles - chemical synthesis</subject><subject>Thiazoles - chemistry</subject><subject>Thiazoles - pharmacology</subject><subject>Tubulin - metabolism</subject><subject>Tubulin Modulators - chemical synthesis</subject><subject>Tubulin Modulators - chemistry</subject><subject>Tubulin Modulators - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc2O0zAUhSMEYsrAghdAdwNiFhn8kx9ndiUwtFKBSi0rhCzHcSYujl1iZzTh2Xg4MrSablhdXd1PR-eeE0UvMbrEiOB3uw5lKE3S_aNohlOC4oSh5HE0Q4iQmGSEnkXPvN8hhCgm9Gl0hrMiRwnCs-jP9yR-u-x0LX47E-N4NBeh1f8WMi0_9q2yoxGdtspfwhy-uFtloDTCe3ANLPRNa0ZYu6BsgNIZ2Wo5sbDRQcF7bWttb2A7VIPRFpa21ZUOrvdXsBltaJXXHoStoRyDC-5OS5jLoG91GMFZ2CijZFA1LIZOWCiFlaqHUhkDq3tDz6MnjTBevTjO8-jb9cdtuYhXXz8ty_kqFpThEJOGZWmNc9pUWVJJmVc4kUUqU1YQJTGTrBKIJkqKqiaqaBpRF5IKlFdCNLSm9Dx6c9Dd9-7XoHzgnfZysiGscoPnGWPplDubwIsDKHvnfa8avu91J_qRY8Tvq-IPVU3sq6PoUHWqPpHHbibg9REQXgrT9NP72p84hnFBWDFx8YHTPqi7h7vof_Isp3nKt-sNT4vrz-zDas3Tk66Qnu_c0Nspu_8Y_Au1kLm3</recordid><startdate>20060921</startdate><enddate>20060921</enddate><creator>Mahboobi, Siavosh</creator><creator>Sellmer, Andreas</creator><creator>Höcher, Heymo</creator><creator>Eichhorn, Emerich</creator><creator>Bär, Thomas</creator><creator>Schmidt, Mathias</creator><creator>Maier, Thomas</creator><creator>Stadlwieser, Josef F</creator><creator>Beckers, Thomas L</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>20060921</creationdate><title>[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines</title><author>Mahboobi, Siavosh ; Sellmer, Andreas ; Höcher, Heymo ; Eichhorn, Emerich ; Bär, Thomas ; Schmidt, Mathias ; Maier, Thomas ; Stadlwieser, Josef F ; Beckers, Thomas L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a381t-2f865d173fb64bcc7b14c95c5892ec18c8ba034ecabd2e9ffad9c3a07baaf3d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Aniline Compounds - chemical synthesis</topic><topic>Aniline Compounds - chemistry</topic><topic>Aniline Compounds - pharmacology</topic><topic>Antineoplastic agents</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Cell Shape - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Colchicine - metabolism</topic><topic>Drug Screening Assays, Antitumor</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure-Activity Relationship</topic><topic>Thiazoles - chemical synthesis</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - pharmacology</topic><topic>Tubulin - metabolism</topic><topic>Tubulin Modulators - chemical synthesis</topic><topic>Tubulin Modulators - chemistry</topic><topic>Tubulin Modulators - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mahboobi, Siavosh</creatorcontrib><creatorcontrib>Sellmer, Andreas</creatorcontrib><creatorcontrib>Höcher, Heymo</creatorcontrib><creatorcontrib>Eichhorn, Emerich</creatorcontrib><creatorcontrib>Bär, Thomas</creatorcontrib><creatorcontrib>Schmidt, Mathias</creatorcontrib><creatorcontrib>Maier, Thomas</creatorcontrib><creatorcontrib>Stadlwieser, Josef F</creatorcontrib><creatorcontrib>Beckers, Thomas L</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>Mahboobi, Siavosh</au><au>Sellmer, Andreas</au><au>Höcher, Heymo</au><au>Eichhorn, Emerich</au><au>Bär, Thomas</au><au>Schmidt, Mathias</au><au>Maier, Thomas</au><au>Stadlwieser, Josef F</au><au>Beckers, Thomas L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>[4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2006-09-21</date><risdate>2006</risdate><volume>49</volume><issue>19</issue><spage>5769</spage><epage>5776</epage><pages>5769-5776</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27kip1 and the influence on microtubule formation were investigated. Considering the significant correlation between the IC50 values of tubulin polymerization inhibition, [3H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. 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| ispartof | Journal of medicinal chemistry, 2006-09, Vol.49 (19), p.5769-5776 |
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| subjects | Aniline Compounds - chemical synthesis Aniline Compounds - chemistry Aniline Compounds - pharmacology Antineoplastic agents Binding Sites Biological and medical sciences Cell Line, Tumor Cell Shape - drug effects Cell Survival - drug effects Colchicine - metabolism Drug Screening Assays, Antitumor General aspects Humans Medical sciences Pharmacology. Drug treatments Structure-Activity Relationship Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacology Tubulin - metabolism Tubulin Modulators - chemical synthesis Tubulin Modulators - chemistry Tubulin Modulators - pharmacology |
| title | [4-(Imidazol-1-yl)thiazol-2-yl]phenylamines. A Novel Class of Highly Potent Colchicine Site Binding Tubulin Inhibitors: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines |
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