Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization
A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by hal...
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| Veröffentlicht in: | Journal of medicinal chemistry 1990-06, Vol.33 (6), p.1721-1728 |
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| container_issue | 6 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 33 |
| creator | Jiang, Jack B Hesson, D. P Dusak, B. A Dexter, D. L Kang, G. J Hamel, E |
| description | A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts. |
| doi_str_mv | 10.1021/jm00168a029 |
| format | Article |
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P ; Dusak, B. A ; Dexter, D. L ; Kang, G. J ; Hamel, E</creator><creatorcontrib>Jiang, Jack B ; Hesson, D. P ; Dusak, B. A ; Dexter, D. L ; Kang, G. J ; Hamel, E</creatorcontrib><description>A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. 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P</creatorcontrib><creatorcontrib>Dusak, B. A</creatorcontrib><creatorcontrib>Dexter, D. L</creatorcontrib><creatorcontrib>Kang, G. J</creatorcontrib><creatorcontrib>Hamel, E</creatorcontrib><title>Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.</description><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</subject><subject>Humans</subject><subject>Leukemia L1210 - drug therapy</subject><subject>Mice</subject><subject>Microtubules - drug effects</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Quinazolines - chemical synthesis</subject><subject>Quinazolines - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Styrenes - chemical synthesis</subject><subject>Styrenes - pharmacology</subject><subject>Tubulin</subject><subject>Tumor Cells, Cultured - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU9v1DAQxSMEKkvhxBnJFwoIAv6TxM4RVUCRVmJRi0BcrIl30vXi2FvboWy_CF-XtLsqHDjNSO-nN6P3iuIxo68Z5ezNeqCUNQoob-8UM1ZzWlaKVneLGaWcl7zh4n7xIKU1pVQwLg6KA06VEhWfFb9Ptz6vMNlEwC9JZ4ML59aAI_gT3AjZBk9CT3iZ8jZu3cVoPVwFZ31ZPRcnL8rgMb0iQDxeEuMgpWsafLaDzSFbc7Mb8AYjgXP0OZHLlTUrYv3KdjaTPHbjZEc2wW0HjPbq5ubD4l4PLuGj_Twsvrx_d3Z8Us4_ffh4_HZeQiXrXGLXVAZF3XDedjUHlLJHUA2rOGuElNBWtTHQm1p0bYstCsClorjkQjEhUBwWRzvfTQwXI6asB5sMOgcew5i0bKVsa6km8OUONDGkFLHXm2gHiFvNqL6uQf9Tw0Q_2duO3YDLW3af-6Q_3euQprD7OAVk01_LVnDFeDNx5Y6zKeOvWx3iD91IIWt9tjjVCzX_vvj2memvE_9sx4NJeh3G6Kfw_vvhH4lSrmU</recordid><startdate>19900601</startdate><enddate>19900601</enddate><creator>Jiang, Jack B</creator><creator>Hesson, D. 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P</creatorcontrib><creatorcontrib>Dusak, B. A</creatorcontrib><creatorcontrib>Dexter, D. L</creatorcontrib><creatorcontrib>Kang, G. J</creatorcontrib><creatorcontrib>Hamel, E</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>Jiang, Jack B</au><au>Hesson, D. P</au><au>Dusak, B. A</au><au>Dexter, D. L</au><au>Kang, G. J</au><au>Hamel, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1990-06-01</date><risdate>1990</risdate><volume>33</volume><issue>6</issue><spage>1721</spage><epage>1728</epage><pages>1721-1728</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A novel series of 2-styrylquinazolin-4(3H-ones which inhibited tubulin polymerization and the growth of L1210 murine leukemia cells was discovered. Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6. These analogues did not substantially interfere with the binding of radiolabeled colchicine, vinblastine, or GTP to tubulin and weakly stimulated GTP hydrolysis uncoupled from polymerization. Several analogues have shown in vivo tumor growth inhibitory activity in the L1210 leukemia model, with the lead compound 5o exhibiting good antitumor activity against murine solid tumors as well as human tumor xenografts.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>2088342</pmid><doi>10.1021/jm00168a029</doi><tpages>8</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1990-06, Vol.33 (6), p.1721-1728 |
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| language | eng |
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| subjects | Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Chemistry Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Humans Leukemia L1210 - drug therapy Mice Microtubules - drug effects Organic chemistry Preparations and properties Quinazolines - chemical synthesis Quinazolines - pharmacology Structure-Activity Relationship Styrenes - chemical synthesis Styrenes - pharmacology Tubulin Tumor Cells, Cultured - drug effects |
| title | Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization |
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