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
Authors: Gonçalves DS, de S Melo SM, Jacomini AP, J V da Silva M, Pianoski KE, Ames FQ, Aguiar RP, Oliveira AF, Volpato H, Bidóia DL, Nakamura CV, Bersani-Amado CA, Back DF, Moura S, Paula FR, Rosa FA
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.
PMID: 32503692 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry - June 8, 2020 Category: Chemistry Authors: Gonçalves DS, de S Melo SM, Jacomini AP, J V da Silva M, Pianoski KE, Ames FQ, Aguiar RP, Oliveira AF, Volpato H, Bidóia DL, Nakamura CV, Bersani-Amado CA, Back DF, Moura S, Paula FR, Rosa FA Tags: Bioorg Med Chem Source Type: research