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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

The molecular basis for coxib inhibition of p38α MAP kinase

2005; Elsevier BV; Volume: 15; Issue: 15 Linguagem: Inglês

10.1016/j.bmcl.2005.05.107

ISSN

1464-3405

Autores

Gilberto M. Sperandio da Silva, Lı́dia Moreira Lima, Carlos Alberto Manssour Fraga, Carlos Maurício R. Sant’Anna, Eliezer J. Barreiro,

Tópico(s)

Synthesis and biological activity

Resumo

In this work, we present the results of two combined approaches, molecular docking and comparative molecular field analysis (CoMFA), to propose how the selective cyclooxygenase-2 inhibitor celecoxib could act as a p38 mitogen-activated protein (MAP) kinase inhibitor. The docking analysis revealed why celecoxib has a less favorable binding energy (ΔG = −12.4 kcal/mol) than the selective p38 MAP kinase (p38 MAPK) inhibitor, SB203580 (ΔG = −22.2 kcal/mol). The CoMFA results revealed unfavorable steric effects that can be related to the predicted lower p38 MAP kinase inhibitory activity of celecoxib. Additionally, FlexX and CoMFA results also suggested that etoricoxib, another selective COX-2 inhibitor, could inhibit p38 MAP kinase.

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