Discovery of a new pyrido[2,3- d ]pyridazine-2,8-dione derivative as a potential anti-inflammatory agent through COX-1/COX-2 dual inhibition.

Autor:	Rosa FA; Departamento de Química, Universidade Estadual de Maringá (UEM) 87030-900 Maringá PR Brazil farosa@uem.br., Gonçalves DS; Departamento de Química, Universidade Estadual de Maringá (UEM) 87030-900 Maringá PR Brazil farosa@uem.br., Pianoski KE; Departamento de Química, Universidade Estadual de Maringá (UEM) 87030-900 Maringá PR Brazil farosa@uem.br., da Silva MJV; Departamento de Química, Universidade Estadual de Maringá (UEM) 87030-900 Maringá PR Brazil farosa@uem.br., 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., Volpato H; Pós-Graduação em Ciências Biológicas, Universidade Estadual de Maringá (UEM) 87020-900 Maringá PR Brazil., Lazarin-Bidóia D; 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.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2024 Feb 08; Vol. 15 (3), pp. 1038-1045. Date of Electronic Publication: 2024 Feb 08 (Print Publication: 2024).
DOI:	10.1039/d3md00604b
Abstrakt:	In this paper, we present the design and synthesis of a novel series of pyrido[2,3- d ]pyridazine-2,8-dione derivatives via the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for in vivo anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its in vitro COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a model for determining selectivity for COX-2. Competing Interests: The authors declare no conflict of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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