Synthesis of novel 3,5,6-trisubstituted 2-pyridone derivatives and evaluation for their anti-inflammatory activity.

Autor: Gonçalves DS; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., de S Melo SM; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Jacomini AP; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., J V da Silva M; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Pianoski KE; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Ames FQ; Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Aguiar RP; Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Oliveira AF; Departamento de Farmácia, Universidade Federal do Pampa (UNIPAMPA), 97500-970 Uruguaiana, RS, Brazil., Volpato H; Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM), 87020-900 Maringá, PR, Brazil., Bidóia DL; Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM), 87020-900 Maringá, PR, Brazil., Nakamura CV; Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM), 87020-900 Maringá, PR, Brazil., Bersani-Amado CA; Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil., Back DF; Departamento de Química, Universidade Federal de Santa Maria (UFSM), 97110-970 Santa Maria, RS, Brazil., Moura S; Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), 295070-560 Caxias do Sul, RS, Brazil., Paula FR; Departamento de Farmácia, Universidade Federal do Pampa (UNIPAMPA), 97500-970 Uruguaiana, RS, Brazil., Rosa FA; Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil. Electronic address: farosa@uem.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2020 Jun 15; Vol. 28 (12), pp. 115549. Date of Electronic Publication: 2020 May 12.
DOI: 10.1016/j.bmc.2020.115549
Abstrakt: The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study.
Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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