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

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dc.creatorAmaral, Daniel Nascimento do
dc.creatorCavalcanti, Bruno Coêlho
dc.creatorBezerra, Daniel Pereira
dc.creatorFerreira, Paulo Michel Pinheiro
dc.creatorCastro, Rosane de Paula
dc.creatorSabino, José Ricardo
dc.creatorMachado, Camila Maria Longo
dc.creatorChammas, Roger
dc.creatorPessoa, Claudia do Ó
dc.creatorSant’Anna, Carlos Mauricio Rabelo
dc.creatorBarreiro, Eliezer Jesus de Lacerda
dc.creatorLima, Lídia Moreira
dc.date.accessioned2018-07-12T15:52:38Z
dc.date.available2018-07-12T15:52:38Z
dc.date.issued2014
dc.description.abstractCancer 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.pt_BR
dc.identifier.citationAMARAL, 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. Docking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analogues. Plos One, San Francisco, v. 9, n. 3, e85380, 2014.pt_BR
dc.identifier.doi10.1371/journal.pone.0085380
dc.identifier.issne- 1420-3049
dc.identifier.urihttp://repositorio.bc.ufg.br/handle/ri/15395
dc.language.isoengpt_BR
dc.publisher.countryEstados unidospt_BR
dc.publisher.departmentInstituto de Física - IF (RG)pt_BR
dc.rightsAcesso Abertopt_BR
dc.titleDocking, synthesis and antiproliferative activity of N-acylhydrazone derivatives designed as combretastatin A4 analoguespt_BR
dc.typeArtigopt_BR

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