Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors

Detalhes bibliográficos
Autor(a) principal: Jacob, Íris T. T.
Data de Publicação: 2021
Outros Autores: 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
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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spelling 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 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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
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str 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
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)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/49783/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/49783/2/Jacob%2c%20Iris%20T.T%20Anti-inflammatory....pdf
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