Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

dc.creatorMoraes, Ana Daura Travassos de Oliveira
dc.creatorMiranda, Mirelly Dianne Santos de
dc.creatorJacob, Íris Trindade Tenório
dc.creatorAmorim, Cézar Augusto da Cruz
dc.creatorMoura, Ricardo Olímpio de
dc.creatorSilva, Simone Ângela Soares da
dc.creatorSoares, Milena Botelho Pereira
dc.creatorAlmeida, Sinara Mônica Vitalino de
dc.creatorSouza, Túlio Ricardo Couto de Lima
dc.creatorOliveira, Jamerson Ferreira de
dc.creatorSilva, Teresinha Gonçalves da
dc.creatorMelo, Cristiane Moutinho Lagos de
dc.creatorMoreira, Diogo Rodrigo Magalhães
dc.creatorLima, Maria do Carmo Alves de
dc.date2018-12-13T13:09:51Z
dc.date2018-12-13T13:09:51Z
dc.date2018
dc.date.accessioned2023-09-27T00:16:12Z
dc.date.available2023-09-27T00:16:12Z
dc.identifierMORAES, 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.
dc.identifier0968-0896
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/30570
dc.identifier10.1016/j.bmc.2018.07.024
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8899148
dc.descriptionBrazilian agencies Fundaçao de Amparo Pesquisa do Estado de Pernambuco (FACEPE, Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq).
dc.descriptionThe 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsopen access
dc.subjectInflamação
dc.subjectN-Acilidrazonas
dc.subjectIndoles
dc.subjectCOX
dc.subjectDocking
dc.subjectInflammation
dc.subjectN-Acylhydrazones
dc.subjectIndoles
dc.subjectCOX
dc.subjectDocking
dc.titleSynthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives
dc.typeArticle


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