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

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

  • Bioorg Med Chem. 2020 Jun 15;28(12):115549. doi: 10.1016/j.bmc.2020.115549.
Davana S Gonçalves 1,  Samara M de S Melo 1,  Andrey P Jacomini 1,  Michael J V da Silva 1,  Karlos E Pianoski 1,  Franciele Q Ames 2,  Rafael P Aguiar 2,  Alisson Felipe Oliveira 3,  Hélito Volpato 4,  Danielle L Bidóia 4,  Celso V Nakamura 4,  Ciomar A Bersani-Amado 2,  Davi F Back 5,  Sidnei Moura 6,  Fávero R Paula 3,  Fernanda A Rosa 7
Affiliations

Affiliations

  • 1 Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil.
  • 2 Departamento de Farmacologia e Terapêutica, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil.
  • 3 Departamento de Farmácia, Universidade Federal do Pampa (UNIPAMPA), 97500-970 Uruguaiana, RS, Brazil.
  • 4 Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM), 87020-900 Maringá, PR, Brazil.
  • 5 Departamento de Química, Universidade Federal de Santa Maria (UFSM), 97110-970 Santa Maria, RS, Brazil.
  • 6 Instituto de Biotecnologia, Universidade de Caxias do Sul (UCS), 295070-560 Caxias do Sul, RS, Brazil.
  • 7 Departamento de Química, Universidade Estadual de Maringá (UEM), 87030-900 Maringá, PR, Brazil. Electronic address: [email protected].
PMID: 32503692 DOI: 10.1016/j.bmc.2020.115549
Abstract

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.

Keywords

2-pyridone; Anti-inflammatory; COXs.

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