Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues

Detalhes bibliográficos
Autor(a) principal: Amaral, Daniel Nascimento do
Data de Publicação: 2014
Outros Autores: Cavalcanti, Bruno C., Bezerra, Daniel P., Ferreira, Paulo Michel P., Castro, Rosane de Paula, Sabino, José Ricardo, Machado, Camila Maria Longo, Chammas, Roger, Pessoa, Claudia, Sant’Anna, Carlos M. R., Barreiro, Eliezer J., Lima, Lídia Moreira
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/9886
Resumo: Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA- 4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on b-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a– r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of b-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values # 18 mM and $4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.
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spelling Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analoguesMicrotúbulosVincaCancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA- 4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on b-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a– r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of b-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values # 18 mM and $4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.Plos One2014-11-24T11:12:21Z2014-11-24T11:12:21Z2014-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfAMARAL, D. N. do et al. Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues. Plos One, v. 9, n. 3, p. e85380, mar. 2014.1932-6203 Onlinehttp://www.repositorio.ufc.br/handle/riufc/9886Amaral, Daniel Nascimento doCavalcanti, Bruno C.Bezerra, Daniel P.Ferreira, Paulo Michel P.Castro, Rosane de PaulaSabino, José RicardoMachado, Camila Maria LongoChammas, RogerPessoa, ClaudiaSant’Anna, Carlos M. R.Barreiro, Eliezer J.Lima, Lídia Moreiraengreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-15T13:06:59Zoai:repositorio.ufc.br:riufc/9886Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:23:09.342374Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
title Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
spellingShingle Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
Amaral, Daniel Nascimento do
Microtúbulos
Vinca
title_short Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
title_full Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
title_fullStr Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
title_full_unstemmed Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
title_sort Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
author Amaral, Daniel Nascimento do
author_facet Amaral, Daniel Nascimento do
Cavalcanti, Bruno C.
Bezerra, Daniel P.
Ferreira, Paulo Michel P.
Castro, Rosane de Paula
Sabino, José Ricardo
Machado, Camila Maria Longo
Chammas, Roger
Pessoa, Claudia
Sant’Anna, Carlos M. R.
Barreiro, Eliezer J.
Lima, Lídia Moreira
author_role author
author2 Cavalcanti, Bruno C.
Bezerra, Daniel P.
Ferreira, Paulo Michel P.
Castro, Rosane de Paula
Sabino, José Ricardo
Machado, Camila Maria Longo
Chammas, Roger
Pessoa, Claudia
Sant’Anna, Carlos M. R.
Barreiro, Eliezer J.
Lima, Lídia Moreira
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Amaral, Daniel Nascimento do
Cavalcanti, Bruno C.
Bezerra, Daniel P.
Ferreira, Paulo Michel P.
Castro, Rosane de Paula
Sabino, José Ricardo
Machado, Camila Maria Longo
Chammas, Roger
Pessoa, Claudia
Sant’Anna, Carlos M. R.
Barreiro, Eliezer J.
Lima, Lídia Moreira
dc.subject.por.fl_str_mv Microtúbulos
Vinca
topic Microtúbulos
Vinca
description Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA- 4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on b-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a– r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of b-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values # 18 mM and $4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.
publishDate 2014
dc.date.none.fl_str_mv 2014-11-24T11:12:21Z
2014-11-24T11:12:21Z
2014-03
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv AMARAL, D. N. do et al. Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues. Plos One, v. 9, n. 3, p. e85380, mar. 2014.
1932-6203 Online
http://www.repositorio.ufc.br/handle/riufc/9886
identifier_str_mv AMARAL, D. N. do et al. Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues. Plos One, v. 9, n. 3, p. e85380, mar. 2014.
1932-6203 Online
url http://www.repositorio.ufc.br/handle/riufc/9886
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Plos One
publisher.none.fl_str_mv Plos One
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
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