Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/49783 |
Resumo: | Brazilian agencies Fundação de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil—Grant no. APQ-0498-4.03/19) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant no. 404264/2016-6). |
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Jacob, Íris T. T.Gomes, Fabiana O. S.Miranda, Mirelly D. S. deAlmeida, Sinara M. V. deCruz Filho, Iranildo J. daPeixoto, Christina A.Silva, · Teresinha G. daMoreira, Diogo R. M.Melo, Cristiane M. L. deOliveira, Jamerson F. deLima, Maria C. A. de2021-11-11T18:36:51Z2021-11-11T18:36:51Z2021JACOB, Íris T. T. et al. Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors. Pharmacological Reports, 2021.1734-1140https://www.arca.fiocruz.br/handle/icict/4978310.1007/s43440-021-00221-7Brazilian agencies Fundação de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil—Grant no. APQ-0498-4.03/19) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant no. 404264/2016-6).Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade de Pernambuco. Faculdade de Ciências, Educação e Tecnologia de Garanhuns. Garanhuns, PE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Universidade da Integração Internacional da Lusofonia Afro-Brasileira. Redenção, CE, Brasil.Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil.Background In this article, a series of 20 new thiosemicarbazone derivatives containing indole were synthesized and evaluated for their anti-inflammatory potential. Methods The compounds were obtained through a synthetic route of only two steps, with yields that varied between 33.6 and 90.4%, and characterized by spectroscopic and spectrometric techniques. Results An initial screening through the lymphoproliferation assay revealed that compounds LT76, LT81, and LT87 were able to inhibit lymphocyte proliferation, with CC50 of 0.56 ± 0.036, 0.9 ± 0.01 and 0.5 ± 0.07 μM, respectively, better results than indomethacin ( CC50 > 12 μM). In addition, these compounds were able to suppress the in-vitro production of TNF-α and NO, in addition to stimulating the production of IL-4. Reinforcing in-vitro assays, the compounds were able to inhibit COX-2 similar to Celecoxib showing greater selectivity for this isoform (LT81 SI: 23.06 versus Celecoxib SI: 11.88). Animal studies showed that compounds LT76 (64.8% inhibition after 6 h), LT81 (89% inhibition after 6 h) and LT87 (100% inhibition after 4 h) were able to suppress edema in mice after inoculation carrageenan with greater potency than indomethacin, and immunohistochemistry revealed that the groups treated with LT76, LT81 and LT87 reduced the expression of COX-2, similar or better results when compared to indomethacin. Complementarily, in-silico studies have shown that these compounds have a good pharmacokinetic profile, for respecting the parameters of Lipinski and Veber, showing their good bioavailability. Conclusions These results demonstrate the potency of thiosemicarbazone derivatives containing indole and confirm their importance as scaffolds of molecules with notorious anti-inflammatory activity.engElsevierTiossemicarbazonaIndoisDroga imunossupressoraFatores imunológicos ·ImunohistoquímicaThiosemicarbazone ·Indole ·Immunosuppressive drugs ·Immunomodulatory agentsCOX-2· ImmunohistochemistryAnti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitorsinfo: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-83097https://www.arca.fiocruz.br/bitstream/icict/49783/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALJacob, Iris T.T Anti-inflammatory....pdfJacob, Iris T.T Anti-inflammatory....pdfapplication/pdf1706152https://www.arca.fiocruz.br/bitstream/icict/49783/2/Jacob%2c%20Iris%20T.T%20Anti-inflammatory....pdf6a6ff92d3488dda6dec1599460da4a7eMD52icict/497832023-03-15 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dc.title.pt_BR.fl_str_mv |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
title |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
spellingShingle |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors Jacob, Íris T. T. Tiossemicarbazona Indois Droga imunossupressora Fatores imunológicos · Imunohistoquímica Thiosemicarbazone · Indole · Immunosuppressive drugs · Immunomodulatory agents COX-2 · Immunohistochemistry |
title_short |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
title_full |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
title_fullStr |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
title_full_unstemmed |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
title_sort |
Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors |
author |
Jacob, Íris T. T. |
author_facet |
Jacob, Íris T. T. Gomes, Fabiana O. S. Miranda, Mirelly D. S. de Almeida, Sinara M. V. de Cruz Filho, Iranildo J. da Peixoto, Christina A. Silva, · Teresinha G. da Moreira, Diogo R. M. Melo, Cristiane M. L. de Oliveira, Jamerson F. de Lima, Maria C. A. de |
author_role |
author |
author2 |
Gomes, Fabiana O. S. Miranda, Mirelly D. S. de Almeida, Sinara M. V. de Cruz Filho, Iranildo J. da Peixoto, Christina A. Silva, · Teresinha G. da Moreira, Diogo R. M. Melo, Cristiane M. L. de Oliveira, Jamerson F. de Lima, Maria C. A. de |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Jacob, Íris T. T. Gomes, Fabiana O. S. Miranda, Mirelly D. S. de Almeida, Sinara M. V. de Cruz Filho, Iranildo J. da Peixoto, Christina A. Silva, · Teresinha G. da Moreira, Diogo R. M. Melo, Cristiane M. L. de Oliveira, Jamerson F. de Lima, Maria C. A. de |
dc.subject.other.pt_BR.fl_str_mv |
Tiossemicarbazona Indois Droga imunossupressora Fatores imunológicos · Imunohistoquímica |
topic |
Tiossemicarbazona Indois Droga imunossupressora Fatores imunológicos · Imunohistoquímica Thiosemicarbazone · Indole · Immunosuppressive drugs · Immunomodulatory agents COX-2 · Immunohistochemistry |
dc.subject.en.pt_BR.fl_str_mv |
Thiosemicarbazone · Indole · Immunosuppressive drugs · Immunomodulatory agents COX-2 · Immunohistochemistry |
description |
Brazilian agencies Fundação de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil—Grant no. APQ-0498-4.03/19) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant no. 404264/2016-6). |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-11-11T18:36:51Z |
dc.date.available.fl_str_mv |
2021-11-11T18:36:51Z |
dc.date.issued.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
JACOB, Íris T. T. et al. Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors. Pharmacological Reports, 2021. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/49783 |
dc.identifier.issn.pt_BR.fl_str_mv |
1734-1140 |
dc.identifier.doi.none.fl_str_mv |
10.1007/s43440-021-00221-7 |
identifier_str_mv |
JACOB, Íris T. T. et al. Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors. Pharmacological Reports, 2021. 1734-1140 10.1007/s43440-021-00221-7 |
url |
https://www.arca.fiocruz.br/handle/icict/49783 |
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eng |
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eng |
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Elsevier |
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Elsevier |
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