Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents

Detalhes bibliográficos
Autor(a) principal: Santos Filho, José Maurício dos
Data de Publicação: 2009
Outros Autores: Leite, Ana Cristina Lima, Oliveira, Boaz Galdino de, Moreira, Diogo Rodrigo Magalhães, Lima, Milena da Silva, Soares, Milena Botelho Pereira, Leite, Lucia Fernanda Cavalcanti da Costa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
DOI: 10.1016/j.bmc.2009.07.068
Texto Completo: https://www.arca.fiocruz.br/handle/icict/9021
Resumo: Universidade Federal de Pernambuco. Departamento de Engenharia Química. Centro de Tecnologia e Geociências. Recife, PE, Brasil
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spelling Santos Filho, José Maurício dosLeite, Ana Cristina LimaOliveira, Boaz Galdino deMoreira, Diogo Rodrigo MagalhãesLima, Milena da SilvaSoares, Milena Botelho PereiraLeite, Lucia Fernanda Cavalcanti da Costa2014-12-01T18:55:39Z2014-12-01T18:55:39Z2009SANTOS FILHO, J. M. dos Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorganic & Medicinal Chemistry, v. 17, n. 18, p. 6682-6691, 2009.1464-3391https://www.arca.fiocruz.br/handle/icict/902110.1016/j.bmc.2009.07.068engElsevier LtdDesign, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agentsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Pernambuco. Departamento de Engenharia Química. Centro de Tecnologia e Geociências. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, BrasilUniversidade Católica de Pernambuco. UNICAP. Recife, PE, BrasilResearch in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we investigated a library of 16 NAH bearing the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold (NAH 3a–h, 4a–h). The in vitro bioactivity against epimastigote and trypomastigote forms of T. cruzi was evaluated, and some NAH under study exhibited antitrypanosomal activity at concentrations that are not toxic to mammalian cells. The series of compounds based on the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold revealed the remarkable importance of each substituent at the phenyl’s 4-position for the inhibitory activity. Non-nitrated compounds 3a and 4e were found to be as potent as the reference drug, Benznidazole. In addition, the molecular origin of the antitrypanosomal properties for these series was investigated using docking studies of the TCC structure.Trypanosoma cruziOxadiazoleOxadiazolePrivileged structuresMolecular dockingCruzainDoença de Chagas/quimioterapiaCisteína Endopeptidases/metabolismoHidrazonas/farmacologiaOxidiazóis/farmacologiaProteínas de Protozoários/metabolismoTripanossomicidas/farmacologiaTrypanosoma cruzi/efeitos de drogasAnimaisSobrevivência Celular/efeitos de drogasHidrazonas/administração & dosagemCamundongosCamundongos Endogâmicos BALB CModelos MolecularesOxidiazóis/administração & dosagemTestes de Sensibilidade ParasitáriaLigação ProteicaProteínas de Protozoários/químicaBaço/citologiaRelação Estrutura-AtividadeTripanossomicidas/administração & dosagemTrypanosoma cruzi/metabolismoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/9021/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALSantos FJM Design, synthesis.....pdfSantos FJM Design, synthesis.....pdfapplication/pdf522130https://www.arca.fiocruz.br/bitstream/icict/9021/2/Santos%20FJM%20Design%2c%20synthesis.....pdf287dfaed572f083f2308fba6f35f1468MD52TEXTSantos FJM Design, synthesis.....pdf.txtSantos FJM Design, synthesis.....pdf.txtExtracted texttext/plain54442https://www.arca.fiocruz.br/bitstream/icict/9021/3/Santos%20FJM%20Design%2c%20synthesis.....pdf.txtffa1ca57a70fa221f492e8cfa5fc831dMD53icict/90212023-03-15 14:33:03.031oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:03Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
title Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
spellingShingle Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
Santos Filho, José Maurício dos
Trypanosoma cruzi
Oxadiazole
Oxadiazole
Privileged structures
Molecular docking
Cruzain
Doença de Chagas/quimioterapia
Cisteína Endopeptidases/metabolismo
Hidrazonas/farmacologia
Oxidiazóis/farmacologia
Proteínas de Protozoários/metabolismo
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos de drogas
Animais
Sobrevivência Celular/efeitos de drogas
Hidrazonas/administração & dosagem
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Oxidiazóis/administração & dosagem
Testes de Sensibilidade Parasitária
Ligação Proteica
Proteínas de Protozoários/química
Baço/citologia
Relação Estrutura-Atividade
Tripanossomicidas/administração & dosagem
Trypanosoma cruzi/metabolismo
title_short Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
title_full Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
title_fullStr Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
title_full_unstemmed Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
title_sort Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents
author Santos Filho, José Maurício dos
author_facet Santos Filho, José Maurício dos
Leite, Ana Cristina Lima
Oliveira, Boaz Galdino de
Moreira, Diogo Rodrigo Magalhães
Lima, Milena da Silva
Soares, Milena Botelho Pereira
Leite, Lucia Fernanda Cavalcanti da Costa
author_role author
author2 Leite, Ana Cristina Lima
Oliveira, Boaz Galdino de
Moreira, Diogo Rodrigo Magalhães
Lima, Milena da Silva
Soares, Milena Botelho Pereira
Leite, Lucia Fernanda Cavalcanti da Costa
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos Filho, José Maurício dos
Leite, Ana Cristina Lima
Oliveira, Boaz Galdino de
Moreira, Diogo Rodrigo Magalhães
Lima, Milena da Silva
Soares, Milena Botelho Pereira
Leite, Lucia Fernanda Cavalcanti da Costa
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Oxadiazole
Oxadiazole
Privileged structures
Molecular docking
Cruzain
topic Trypanosoma cruzi
Oxadiazole
Oxadiazole
Privileged structures
Molecular docking
Cruzain
Doença de Chagas/quimioterapia
Cisteína Endopeptidases/metabolismo
Hidrazonas/farmacologia
Oxidiazóis/farmacologia
Proteínas de Protozoários/metabolismo
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos de drogas
Animais
Sobrevivência Celular/efeitos de drogas
Hidrazonas/administração & dosagem
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Oxidiazóis/administração & dosagem
Testes de Sensibilidade Parasitária
Ligação Proteica
Proteínas de Protozoários/química
Baço/citologia
Relação Estrutura-Atividade
Tripanossomicidas/administração & dosagem
Trypanosoma cruzi/metabolismo
dc.subject.decs.pt_BR.fl_str_mv Doença de Chagas/quimioterapia
Cisteína Endopeptidases/metabolismo
Hidrazonas/farmacologia
Oxidiazóis/farmacologia
Proteínas de Protozoários/metabolismo
Tripanossomicidas/farmacologia
Trypanosoma cruzi/efeitos de drogas
Animais
Sobrevivência Celular/efeitos de drogas
Hidrazonas/administração & dosagem
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Oxidiazóis/administração & dosagem
Testes de Sensibilidade Parasitária
Ligação Proteica
Proteínas de Protozoários/química
Baço/citologia
Relação Estrutura-Atividade
Tripanossomicidas/administração & dosagem
Trypanosoma cruzi/metabolismo
description Universidade Federal de Pernambuco. Departamento de Engenharia Química. Centro de Tecnologia e Geociências. Recife, PE, Brasil
publishDate 2009
dc.date.issued.fl_str_mv 2009
dc.date.accessioned.fl_str_mv 2014-12-01T18:55:39Z
dc.date.available.fl_str_mv 2014-12-01T18:55:39Z
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.citation.fl_str_mv SANTOS FILHO, J. M. dos Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorganic & Medicinal Chemistry, v. 17, n. 18, p. 6682-6691, 2009.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/9021
dc.identifier.issn.none.fl_str_mv 1464-3391
dc.identifier.doi.none.fl_str_mv 10.1016/j.bmc.2009.07.068
identifier_str_mv SANTOS FILHO, J. M. dos Design, synthesis and cruzain docking of 3-(4-substituted-aryl)-1,2,4-oxadiazole-N-acylhydrazones as anti-Trypanosoma cruzi agents. Bioorganic & Medicinal Chemistry, v. 17, n. 18, p. 6682-6691, 2009.
1464-3391
10.1016/j.bmc.2009.07.068
url https://www.arca.fiocruz.br/handle/icict/9021
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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