Author | Moraes, Ana Daura Travassos de Oliveira | |
Author | Miranda, Mirelly Dianne Santos de | |
Author | Jacob, Íris Trindade Tenório | |
Author | Amorim, Cézar Augusto da Cruz | |
Author | Moura, Ricardo Olímpio de | |
Author | Silva, Simone Ângela Soares da | |
Author | Soares, Milena Botelho Pereira | |
Author | Almeida, Sinara Mônica Vitalino de | |
Author | Souza, Túlio Ricardo Couto de Lima | |
Author | Oliveira, Jamerson Ferreira de | |
Author | Silva, Teresinha Gonçalves da | |
Author | Melo, Cristiane Moutinho Lagos de | |
Author | Moreira, Diogo Rodrigo Magalhães | |
Author | Lima, Maria do Carmo Alves de | |
Access date | 2018-12-13T13:09:51Z | |
Available date | 2018-12-13T13:09:51Z | |
Document date | 2018 | |
Citation | MORAES, A. D. T. O. et al. Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives. Bioorganic and Medicinal Chemistry, jul. 2018. | pt_BR |
ISSN | 0968-0896 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/30570 | |
Sponsorship | Brazilian agencies Fundaçao de
Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil) and
Conselho Nacional de Desenvolvimento Científico e Tecnologico
(CNPq). | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Inflamação | pt_BR |
Subject in Portuguese | N-Acilidrazonas | pt_BR |
Subject in Portuguese | Indoles | pt_BR |
Subject in Portuguese | COX | pt_BR |
Subject in Portuguese | Docking | pt_BR |
Title | Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.bmc.2018.07.024 | |
Abstract | The objective of this work was to obtain and evaluate anti-inflammatory in vitro, in vivo and in silico potential of novel indole-N-acylhydrazone derivatives. In total, 10 new compounds (3a-j) were synthesized in satisfactory yields, through a condensation reaction in a single synthesis step. In the lymphoproliferation assay, using mice splenocytes, 3a and 3b showed inhibition of lymphocyte proliferation of 62.7% (±3.5) and 50.7% (±2), respectively, while dexamethasone presented an inhibition of 74.6% (±2.4). Moreover, compound 3b induced higher Th2 cytokines production in mice splenocytes cultures. The results for COX inhibition assays showed that compound 3b is a selective COX-2 inhibitor, but with less potency when compared to celecoxib, and compound 3a not presented selectivity towards COX-2. The molecular docking results suggest compounds 3a and 3b interact with the active site of COX-2 in similar conformations, but not with the active site of COX-1, and this may be the main reason to the COX-2 selectivity of compound 3b. In vivo carrageenan-induced paw edema assays were adopted for the confirmation of the anti-inflammatory activity. Compound 3b showed better results in suppressing edema at all tested concentrations and was able to induce an edema inhibition of 100% after 5 h of carrageenan injection at the 30 mg kg-1 dosage, corroborating with the COX inhibition and lymphoproliferation results. I addition to our experimental results, in silico analysis suggest that compounds 3a and 3b present a well-balanced profile between pharmacodynamics and pharmacokinetics. Thus, our preliminary results revealed the potentiality of a new COX-2 selective derivative in the modulation of the inflammatory process. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade Estadual da Paraíba. Departamento de Farmácia. Campina Grande, PB, Brasil. | pt_BR |
Affilliation | Universidade Estadual da Paraíba. Departamento de Farmácia. Campina Grande, PB, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade de Pernambuco. Faculdade de Ciências, Educação e Tecnologia de Garanhuns. Garanhuns, PE, Brasil | pt_BR |
Affilliation | Universidade Federal Rural de Pernambuco. Unidade Acadêmica de Serra Talhada. Serra Talhada, PE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. 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. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal de Pernambuco. Departamento de Antibióticos. Recife, PE, Brasil. | pt_BR |
Subject | Inflammation | pt_BR |
Subject | N-Acylhydrazones | pt_BR |
Subject | Indoles | pt_BR |
Subject | COX | pt_BR |
Subject | Docking | pt_BR |