(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
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , |
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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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 |
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https://www.arca.fiocruz.br/handle/icict/42042 |
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por |
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MDPI |
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