Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009000400013 |
Resumo: | An important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity. |
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Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studiescancerdrug designdiscodermolidemicrotubule²-tubulinAn important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity.Sociedade Brasileira de Química2009-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009000400013Journal of the Brazilian Chemical Society v.20 n.4 2009reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.1590/S0103-50532009000400013info:eu-repo/semantics/openAccessSalum,Lívia B.Dias,Luiz C.Andricopulo,Adriano D.eng2009-06-10T00:00:00Zoai:scielo:S0103-50532009000400013Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2009-06-10T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
title |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
spellingShingle |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies Salum,Lívia B. cancer drug design discodermolide microtubule ²-tubulin |
title_short |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
title_full |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
title_fullStr |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
title_full_unstemmed |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
title_sort |
Structural and chemical basis for anticancer activity of a series of²-tubulin ligands: molecular modeling and 3D QSAR studies |
author |
Salum,Lívia B. |
author_facet |
Salum,Lívia B. Dias,Luiz C. Andricopulo,Adriano D. |
author_role |
author |
author2 |
Dias,Luiz C. Andricopulo,Adriano D. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Salum,Lívia B. Dias,Luiz C. Andricopulo,Adriano D. |
dc.subject.por.fl_str_mv |
cancer drug design discodermolide microtubule ²-tubulin |
topic |
cancer drug design discodermolide microtubule ²-tubulin |
description |
An important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009000400013 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009000400013 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0103-50532009000400013 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.20 n.4 2009 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
_version_ |
1750318169822593024 |