In vitro characterization of the enzymes involved in the metabolism of 1-furan-2-yl-3-pyridin-2-yl-propenone, an anti-inflammatory propenone compound.
Arch Pharm Res
; 31(6): 764-70, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18563359
ABSTRACT
Carbonyl reduction is a significant step in the phase I biotransformation of a great variety of aromatic, alicyclic and aliphatic carbonyl compounds. 1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has been shown to have anti-inflammatory activity as it inhibits the production of nitric oxide and tumor necrosis factor-beta. In the present study, the metabolic fate and possible involvement of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) and carbonyl reductase (CBR) in the metabolism of FPP-3 were investigated in rat liver subcellular fractions. When FPP-3 was incubated with rat liver subcellular fractions in the presence of beta-NADPH, two major peaks were detected by reduction on the propenone M1 (1-furan-2-yl-3-pyridin-2-yl-propan-1-one) and M2 (1-furan-2-yl-3-pyridin-2-yl-propan-1-ol). Inhibitors of CBR, such as quercitrin, ethacrynic acid and menadione, significantly increased the formation of M1, but effectively inhibited the formation of M2 in subcellular fractions. Meanwhile, 18beta-glycyrrhetinic acid, a selective inhibitor of 11beta-HSD, marginally inhibited the reduction of FPP-3 in microsomes. A good correlation was observed between the formation of M2 and CBR activity with either 4-pyridine carboxaldehyde (r=0.72) or D,L-glyceraldehyde (r=0.63) as substrates in the cytosol. These results indicated that FPP-3 might be metabolized by cytosolic CBR and uncharacterized microsomal reductase(s) in rat liver.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propano
/
Piridinas
/
Oxidorreductasas de Alcohol
/
Furanos
/
Hígado
/
Antiinflamatorios
Límite:
Animals
Idioma:
En
Revista:
Arch Pharm Res
Año:
2008
Tipo del documento:
Article