| Author | Jacob, Íris T. T. | |
| Author | Gomes, Fabiana O. S. | |
| Author | Miranda, Mirelly D. S. de | |
| Author | Almeida, Sinara M. V. de | |
| Author | Cruz Filho, Iranildo J. da | |
| Author | Peixoto, Christina A. | |
| Author | Silva, · Teresinha G. da | |
| Author | Moreira, Diogo R. M. | |
| Author | Melo, Cristiane M. L. de | |
| Author | Oliveira, Jamerson F. de | |
| Author | Lima, Maria C. A. de | |
| Access date | 2021-11-11T18:36:51Z | |
| Available date | 2021-11-11T18:36:51Z | |
| Document date | 2021 | |
| Citation | JACOB, Íris T. T. et al. Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors. Pharmacological Reports, 2021. | pt_BR |
| ISSN | 1734-1140 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49783 | |
| Sponsorship | 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). | pt_BR |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Tiossemicarbazona | pt_BR |
| Subject in Portuguese | Indois | pt_BR |
| Subject in Portuguese | Droga imunossupressora | pt_BR |
| Subject in Portuguese | Fatores imunológicos · | pt_BR |
| Subject in Portuguese | Imunohistoquímica | pt_BR |
| Title | Anti‑inflammatory activity of novel thiosemicarbazone compounds indole‑based as COX inhibitors | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1007/s43440-021-00221-7 | |
| Abstract | 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. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade de Pernambuco. Faculdade de Ciências, Educação e Tecnologia de Garanhuns. Garanhuns, PE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade da Integração Internacional da Lusofonia Afro-Brasileira. Redenção, CE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
| Subject | Thiosemicarbazone · | pt_BR |
| Subject | Indole · | pt_BR |
| Subject | Immunosuppressive drugs · | pt_BR |
| Subject | Immunomodulatory agents | pt_BR |
| Subject | COX-2 | pt_BR |
| Subject | · Immunohistochemistry | pt_BR |
