Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

Detalhes bibliográficos
Autor(a) principal: Moraes, Ana Daura Travassos de Oliveira
Data de Publicação: 2018
Outros Autores: Miranda, Mirelly Dianne Santos de, Jacob, Íris Trindade Tenório, Amorim, Cézar Augusto da Cruz, Moura, Ricardo Olímpio de, Silva, Simone Ângela Soares da, Soares, Milena Botelho Pereira, Almeida, Sinara Mônica Vitalino de, Souza, Túlio Ricardo Couto de Lima, Oliveira, Jamerson Ferreira de, Silva, Teresinha Gonçalves da, Melo, Cristiane Moutinho Lagos de, Moreira, Diogo Rodrigo Magalhães, Lima, Maria do Carmo Alves de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/30570
Resumo: Brazilian agencies Fundaçao de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq).
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spelling Moraes, Ana Daura Travassos de OliveiraMiranda, Mirelly Dianne Santos deJacob, Íris Trindade TenórioAmorim, Cézar Augusto da CruzMoura, Ricardo Olímpio deSilva, Simone Ângela Soares daSoares, Milena Botelho PereiraAlmeida, Sinara Mônica Vitalino deSouza, Túlio Ricardo Couto de LimaOliveira, Jamerson Ferreira deSilva, Teresinha Gonçalves daMelo, Cristiane Moutinho Lagos deMoreira, Diogo Rodrigo MagalhãesLima, Maria do Carmo Alves de2018-12-13T13:09:51Z2018-12-13T13:09:51Z2018MORAES, A. D. T. O. et al. Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives. Bioorganic and Medicinal Chemistry, jul. 2018.0968-0896https://www.arca.fiocruz.br/handle/icict/3057010.1016/j.bmc.2018.07.024Brazilian agencies Fundaçao de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq).Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Estadual da Paraíba. Departamento de Farmácia. Campina Grande, PB, Brasil.Universidade Estadual da Paraíba. Departamento de Farmácia. Campina Grande, PB, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.Universidade de Pernambuco. Faculdade de Ciências, Educação e Tecnologia de Garanhuns. Garanhuns, PE, BrasilUniversidade Federal Rural de Pernambuco. Unidade Acadêmica de Serra Talhada. Serra Talhada, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5 h of carrageenan injection at the 30 mg kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process.engElsevierInflamaçãoN-AcilidrazonasIndolesCOXDockingInflammationN-AcylhydrazonesIndolesCOXDockingSynthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivativesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/30570/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMoraes AD. Synthesis, in vitro... 2018.pdfMoraes AD. 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dc.title.pt_BR.fl_str_mv Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
title Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
spellingShingle Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
Moraes, Ana Daura Travassos de Oliveira
Inflamação
N-Acilidrazonas
Indoles
COX
Docking
Inflammation
N-Acylhydrazones
Indoles
COX
Docking
title_short Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
title_full Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
title_fullStr Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
title_full_unstemmed Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
title_sort Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
author Moraes, Ana Daura Travassos de Oliveira
author_facet Moraes, Ana Daura Travassos de Oliveira
Miranda, Mirelly Dianne Santos de
Jacob, Íris Trindade Tenório
Amorim, Cézar Augusto da Cruz
Moura, Ricardo Olímpio de
Silva, Simone Ângela Soares da
Soares, Milena Botelho Pereira
Almeida, Sinara Mônica Vitalino de
Souza, Túlio Ricardo Couto de Lima
Oliveira, Jamerson Ferreira de
Silva, Teresinha Gonçalves da
Melo, Cristiane Moutinho Lagos de
Moreira, Diogo Rodrigo Magalhães
Lima, Maria do Carmo Alves de
author_role author
author2 Miranda, Mirelly Dianne Santos de
Jacob, Íris Trindade Tenório
Amorim, Cézar Augusto da Cruz
Moura, Ricardo Olímpio de
Silva, Simone Ângela Soares da
Soares, Milena Botelho Pereira
Almeida, Sinara Mônica Vitalino de
Souza, Túlio Ricardo Couto de Lima
Oliveira, Jamerson Ferreira de
Silva, Teresinha Gonçalves da
Melo, Cristiane Moutinho Lagos de
Moreira, Diogo Rodrigo Magalhães
Lima, Maria do Carmo Alves de
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Moraes, Ana Daura Travassos de Oliveira
Miranda, Mirelly Dianne Santos de
Jacob, Íris Trindade Tenório
Amorim, Cézar Augusto da Cruz
Moura, Ricardo Olímpio de
Silva, Simone Ângela Soares da
Soares, Milena Botelho Pereira
Almeida, Sinara Mônica Vitalino de
Souza, Túlio Ricardo Couto de Lima
Oliveira, Jamerson Ferreira de
Silva, Teresinha Gonçalves da
Melo, Cristiane Moutinho Lagos de
Moreira, Diogo Rodrigo Magalhães
Lima, Maria do Carmo Alves de
dc.subject.other.pt_BR.fl_str_mv Inflamação
N-Acilidrazonas
Indoles
COX
Docking
topic Inflamação
N-Acilidrazonas
Indoles
COX
Docking
Inflammation
N-Acylhydrazones
Indoles
COX
Docking
dc.subject.en.pt_BR.fl_str_mv Inflammation
N-Acylhydrazones
Indoles
COX
Docking
description Brazilian agencies Fundaçao de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-12-13T13:09:51Z
dc.date.available.fl_str_mv 2018-12-13T13:09:51Z
dc.date.issued.fl_str_mv 2018
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 MORAES, A. D. T. O. et al. Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives. Bioorganic and Medicinal Chemistry, jul. 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/30570
dc.identifier.issn.pt_BR.fl_str_mv 0968-0896
dc.identifier.doi.none.fl_str_mv 10.1016/j.bmc.2018.07.024
identifier_str_mv MORAES, A. D. T. O. et al. Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives. Bioorganic and Medicinal Chemistry, jul. 2018.
0968-0896
10.1016/j.bmc.2018.07.024
url https://www.arca.fiocruz.br/handle/icict/30570
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.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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