Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents
Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of t...
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| Veröffentlicht in: | European journal of medicinal chemistry 2013-02, Vol.60, p.305-324 |
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| creator | Kumar, A. Suresh Reddy, M. Amarnath Jain, Nishant Kishor, Chandan Murthy, T. Ramalinga Ramesh, Deepa Supriya, Bhukya Addlagatta, Anthony Kalivendi, Shasi V. Sreedhar, B. |
| description | Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.
[Display omitted] Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. Effective compounds interacted at colchicine binding site of tubulin.
► Twenty two biaryl aryl stilbenes/ethylenes were designed and synthesized. ► Most of the compounds inhibited cell proliferation against 4 cancer cell lines. ► Potent derivatives arrested cells at G2/M phase, disrupted microtubule network. ► Investigated compounds dock at the colchicine binding site of the tubulin. |
| doi_str_mv | 10.1016/j.ejmech.2012.12.008 |
| format | Article |
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[Display omitted] Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. Effective compounds interacted at colchicine binding site of tubulin.
► Twenty two biaryl aryl stilbenes/ethylenes were designed and synthesized. ► Most of the compounds inhibited cell proliferation against 4 cancer cell lines. ► Potent derivatives arrested cells at G2/M phase, disrupted microtubule network. ► Investigated compounds dock at the colchicine binding site of the tubulin.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2012.12.008</identifier><identifier>PMID: 23313639</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Antimicrotubule agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antiproliferative activity ; Biaryl aryl ethylenes ; Biaryl aryl stilbenes ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Dose-Response Relationship, Drug ; Drug Design ; Drug Screening Assays, Antitumor ; Ethylenes - chemical synthesis ; Ethylenes - chemistry ; Ethylenes - pharmacology ; HeLa Cells ; Humans ; Models, Molecular ; Molecular Structure ; Stilbenes - chemical synthesis ; Stilbenes - chemistry ; Stilbenes - pharmacology ; Structure-Activity Relationship ; Tubulin polymerization ; Tumor Cells, Cultured</subject><ispartof>European journal of medicinal chemistry, 2013-02, Vol.60, p.305-324</ispartof><rights>2012 Elsevier Masson SAS</rights><rights>Copyright © 2012 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-16d18a188004f04c424aebfa87dccef276cf7eedb3090c98a16fd51d0ad141df3</citedby><cites>FETCH-LOGICAL-c362t-16d18a188004f04c424aebfa87dccef276cf7eedb3090c98a16fd51d0ad141df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2012.12.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23313639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, A. Suresh</creatorcontrib><creatorcontrib>Reddy, M. Amarnath</creatorcontrib><creatorcontrib>Jain, Nishant</creatorcontrib><creatorcontrib>Kishor, Chandan</creatorcontrib><creatorcontrib>Murthy, T. Ramalinga</creatorcontrib><creatorcontrib>Ramesh, Deepa</creatorcontrib><creatorcontrib>Supriya, Bhukya</creatorcontrib><creatorcontrib>Addlagatta, Anthony</creatorcontrib><creatorcontrib>Kalivendi, Shasi V.</creatorcontrib><creatorcontrib>Sreedhar, B.</creatorcontrib><title>Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.
[Display omitted] Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. Effective compounds interacted at colchicine binding site of tubulin.
► Twenty two biaryl aryl stilbenes/ethylenes were designed and synthesized. ► Most of the compounds inhibited cell proliferation against 4 cancer cell lines. ► Potent derivatives arrested cells at G2/M phase, disrupted microtubule network. ► Investigated compounds dock at the colchicine binding site of the tubulin.</description><subject>Antimicrotubule agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferative activity</subject><subject>Biaryl aryl ethylenes</subject><subject>Biaryl aryl stilbenes</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Ethylenes - chemical synthesis</subject><subject>Ethylenes - chemistry</subject><subject>Ethylenes - pharmacology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Stilbenes - chemical synthesis</subject><subject>Stilbenes - chemistry</subject><subject>Stilbenes - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Tubulin polymerization</subject><subject>Tumor Cells, Cultured</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kNtKAzEQQIMotlb_QGQffdnt5NLt9kWQeoWCIPocssmkTdlL3WSF_o3f4peZWvVRGGYSOJPJHELOKWQUaD5eZ7iuUa8yBpRlMQCKAzKk07xIOZuIQzIExng6YVwMyIn3awCY5ADHZMA4pzznsyF5vkHvlk2iGpP4bRNW8eqT1ialU922Sr6TD64qsUE_xrDaVrtTovznh2qCq53u2tCXfYWJWmIT_Ck5sqryePZTR-T17vZl_pAunu4f59eLVPOchZTmhhaKFgWAsCC0YEJhaVUxNVqjZdNc2ymiKTnMQM8imlszoQaUoYIay0fkcv_upmvfevRB1s5rrCrVYNt7STllBZ9RJiIq9mj8q_cdWrnpXB13kxTkzqZcy71NubMpY0Sbse3iZ0Jf1mj-mn71ReBqD2Dc891hJ7122Gg0rkMdpGnd_xO-AOx5ihY</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Kumar, A. Suresh</creator><creator>Reddy, M. Amarnath</creator><creator>Jain, Nishant</creator><creator>Kishor, Chandan</creator><creator>Murthy, T. Ramalinga</creator><creator>Ramesh, Deepa</creator><creator>Supriya, Bhukya</creator><creator>Addlagatta, Anthony</creator><creator>Kalivendi, Shasi V.</creator><creator>Sreedhar, B.</creator><general>Elsevier Masson SAS</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></search><sort><creationdate>201302</creationdate><title>Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents</title><author>Kumar, A. Suresh ; Reddy, M. Amarnath ; Jain, Nishant ; Kishor, Chandan ; Murthy, T. Ramalinga ; Ramesh, Deepa ; Supriya, Bhukya ; Addlagatta, Anthony ; Kalivendi, Shasi V. ; Sreedhar, B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-16d18a188004f04c424aebfa87dccef276cf7eedb3090c98a16fd51d0ad141df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antimicrotubule agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiproliferative activity</topic><topic>Biaryl aryl ethylenes</topic><topic>Biaryl aryl stilbenes</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Ethylenes - chemical synthesis</topic><topic>Ethylenes - chemistry</topic><topic>Ethylenes - pharmacology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Stilbenes - chemical synthesis</topic><topic>Stilbenes - chemistry</topic><topic>Stilbenes - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Tubulin polymerization</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, A. Suresh</creatorcontrib><creatorcontrib>Reddy, M. Amarnath</creatorcontrib><creatorcontrib>Jain, Nishant</creatorcontrib><creatorcontrib>Kishor, Chandan</creatorcontrib><creatorcontrib>Murthy, T. Ramalinga</creatorcontrib><creatorcontrib>Ramesh, Deepa</creatorcontrib><creatorcontrib>Supriya, Bhukya</creatorcontrib><creatorcontrib>Addlagatta, Anthony</creatorcontrib><creatorcontrib>Kalivendi, Shasi V.</creatorcontrib><creatorcontrib>Sreedhar, B.</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><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, A. Suresh</au><au>Reddy, M. Amarnath</au><au>Jain, Nishant</au><au>Kishor, Chandan</au><au>Murthy, T. Ramalinga</au><au>Ramesh, Deepa</au><au>Supriya, Bhukya</au><au>Addlagatta, Anthony</au><au>Kalivendi, Shasi V.</au><au>Sreedhar, B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2013-02</date><risdate>2013</risdate><volume>60</volume><spage>305</spage><epage>324</epage><pages>305-324</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><abstract>Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.
[Display omitted] Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. Effective compounds interacted at colchicine binding site of tubulin.
► Twenty two biaryl aryl stilbenes/ethylenes were designed and synthesized. ► Most of the compounds inhibited cell proliferation against 4 cancer cell lines. ► Potent derivatives arrested cells at G2/M phase, disrupted microtubule network. ► Investigated compounds dock at the colchicine binding site of the tubulin.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>23313639</pmid><doi>10.1016/j.ejmech.2012.12.008</doi><tpages>20</tpages></addata></record> |
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| ispartof | European journal of medicinal chemistry, 2013-02, Vol.60, p.305-324 |
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| subjects | Antimicrotubule agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antiproliferative activity Biaryl aryl ethylenes Biaryl aryl stilbenes Cell Proliferation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug Drug Design Drug Screening Assays, Antitumor Ethylenes - chemical synthesis Ethylenes - chemistry Ethylenes - pharmacology HeLa Cells Humans Models, Molecular Molecular Structure Stilbenes - chemical synthesis Stilbenes - chemistry Stilbenes - pharmacology Structure-Activity Relationship Tubulin polymerization Tumor Cells, Cultured |
| title | Design and synthesis of biaryl aryl stilbenes/ethylenes as antimicrotubule agents |
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