(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

Detalhes bibliográficos
Autor(a) principal: Silva, Pablo
Data de Publicação: 2020
Outros Autores: Almeida, Maria de, Silva, Jamire, Albino, Sonaly, Espírito Santo, Renan, Lima, Maria, Villarreal, Cristiane, Moura, Ricardo, Santos, Vanda
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/42042
Resumo: Fundação de Amparo à Pesquisa do Estado da Paraiba (FAPESQ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) with collaboration from the Universidade Federal da Bahia (UFBA).
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spelling Silva, PabloAlmeida, Maria deSilva, JamireAlbino, SonalyEspírito Santo, RenanLima, MariaVillarreal, CristianeMoura, RicardoSantos, Vanda2020-07-02T14:23:54Z2020-07-02T14:23:54Z2020SILVA, Pablo et al. (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential. International Journal of Molecular Sciences, v. 21, p, 2591, 2020.1661-6596https://www.arca.fiocruz.br/handle/icict/4204210.3390/ijms21072591Fundação de Amparo à Pesquisa do Estado da Paraiba (FAPESQ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) with collaboration from the Universidade Federal da Bahia (UFBA).Universidade Estadual da Paraíba. Programa de Pós-Graduação em Ciências Farmacêuticas. Campina Grande, PB, Brasil / Universidade Estadual da Paraíba. Laboratório de Ensaios Farmacológicos. Departamento de Farmácia. Campina Grande, PB, Brasil / Universidade Estadual da Paraíba. Laboratório de Desenvolvimento e Síntese de Fármacos. Departamento de Farmácia. Campina Grande, PB, Brasil.Universidade Estadual da Paraíba. Laboratório de Ensaios Farmacológicos. Departamento de Farmácia. Campina Grande, PB, Brasil.Universidade Estadual da Paraíba. Laboratório de Desenvolvimento e Síntese de Fármacos. Departamento de Farmácia. Campina Grande, PB, Brasil / Universidade Federal de Pernambuco. Programa de Pós-Graduação em Ciências Farmacêuticas. Recife, PE, Brasil.Universidade Estadual da Paraíba. Programa de Pós-Graduação em Ciências Farmacêuticas. Campina Grande, PB, Brasil / Universidade Estadual da Paraíba. Laboratório de Desenvolvimento e Síntese de Fármacos. Departamento de Farmácia. Campina Grande, PB, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Universidade Federal de Pernambuco. Programa de Pós-Graduação em Ciências Farmacêuticas. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.Universidade Estadual da Paraíba. Programa de Pós-Graduação em Ciências Farmacêuticas. Campina Grande, PB, Brasil / Universidade Estadual da Paraíba. Laboratório de Desenvolvimento e Síntese de Fármacos. Departamento de Farmácia. Campina Grande, PB, Brasil.Universidade Estadual da Paraíba. Programa de Pós-Graduação em Ciências Farmacêuticas. Campina Grande, PB, Brasil / Universidade Estadual da Paraíba. Laboratório de Ensaios Farmacológicos. Departamento de Farmácia. Campina Grande, PB, Brasil.The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg-1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2-6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.porMDPICitocinasEdemaDinoprostoneCytokinesPaw edemaPGE2Phenylacrylamide(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potentialinfo: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/42042/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSilva Pablo (E)-2-Cyano-3-.pdfSilva Pablo 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dc.title.pt_BR.fl_str_mv (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
title (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
spellingShingle (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
Silva, Pablo
Citocinas
Edema
Dinoprostone
Cytokines
Paw edema
PGE2
Phenylacrylamide
title_short (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
title_full (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
title_fullStr (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
title_full_unstemmed (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
title_sort (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential
author Silva, Pablo
author_facet Silva, Pablo
Almeida, Maria de
Silva, Jamire
Albino, Sonaly
Espírito Santo, Renan
Lima, Maria
Villarreal, Cristiane
Moura, Ricardo
Santos, Vanda
author_role author
author2 Almeida, Maria de
Silva, Jamire
Albino, Sonaly
Espírito Santo, Renan
Lima, Maria
Villarreal, Cristiane
Moura, Ricardo
Santos, Vanda
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silva, Pablo
Almeida, Maria de
Silva, Jamire
Albino, Sonaly
Espírito Santo, Renan
Lima, Maria
Villarreal, Cristiane
Moura, Ricardo
Santos, Vanda
dc.subject.other.pt_BR.fl_str_mv Citocinas
Edema
Dinoprostone
topic Citocinas
Edema
Dinoprostone
Cytokines
Paw edema
PGE2
Phenylacrylamide
dc.subject.en.pt_BR.fl_str_mv Cytokines
Paw edema
PGE2
Phenylacrylamide
description Fundação de Amparo à Pesquisa do Estado da Paraiba (FAPESQ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) with collaboration from the Universidade Federal da Bahia (UFBA).
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-07-02T14:23:54Z
dc.date.available.fl_str_mv 2020-07-02T14:23:54Z
dc.date.issued.fl_str_mv 2020
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 SILVA, Pablo et al. (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential. International Journal of Molecular Sciences, v. 21, p, 2591, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/42042
dc.identifier.issn.pt_BR.fl_str_mv 1661-6596
dc.identifier.doi.pt_BR.fl_str_mv 10.3390/ijms21072591
identifier_str_mv SILVA, Pablo et al. (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential. International Journal of Molecular Sciences, v. 21, p, 2591, 2020.
1661-6596
10.3390/ijms21072591
url https://www.arca.fiocruz.br/handle/icict/42042
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language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv MDPI
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dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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