Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , |
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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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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1813028781247430656 |