4-Fluoro-2-methoxyphenol, an apocynin analog with enhanced inhibitory effect on leukocyte oxidant production and phagocytosis
Carregando...
Arquivos
Data
2011-06-25
Autores
de Almeida, Ana Carolina [UNESP]
Marques, Otavio Cabral
Arslanian, Christina
Condino-Neto, Antonio
Ximenes, Valdecir Farias [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Elsevier B.V.
Resumo
Apocynin, a methoxy-substituted catechol (4-hydroxy-3-methoxyacetophenone), originally extracted from the roots of Picrorhiza kurroa, has been extensively used as a non-toxic inhibitor of the multienzymatic complex NADPH oxidase. We discovered that the analogous methoxy-substituted catechol, 4-Fluoro-2-methoxyphenol (F-apocynin), in which the acetyl group present in apocynin was changed to a fluorine atom, was significantly more potent as an inhibitor of NADPH oxidase activity, myeloperoxidase (MPO) chlorinating activity and phagocytosis of microorganisms by neutrophils; it was also as potent as apocynin in inhibiting tumor necrosis factor-alpha (TNF alpha) release by peripheral blood mononuclear cells. We attribute the increased potency of F-apocynin to its increased lipophilicity, which could facilitate the passage of the drug through the cell membrane. The inhibition of MPO chlorination activity, phagocytosis and TNF alpha release shows that apocynin and F-apocynin actions are not restricted to reactive oxygen species inhibition, but further studies are needed to clarify if these mechanisms are related. Like apocynin, F-apocynin did not show cell toxicity, and is a strong candidate for use in the treatment of inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.
Descrição
Palavras-chave
Apocynin, Neutrophil, Myeloperoxidase, NADPH oxidase, TNF alpha, Phagocytosis
Como citar
European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 660, n. 2-3, p. 445-453, 2011.