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-β. In the present study, the metabolic fate and possible involvement of 11β-hydroxysteroid dehydrogenase (11β-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 β-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, 18β-glycyrrhetinic acid, a selective inhibitor of 11β-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.
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Lee, S.K., Kim, J.H., Seo, Y.M. et al. 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, 764–770 (2008). https://doi.org/10.1007/s12272-001-1224-3
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DOI: https://doi.org/10.1007/s12272-001-1224-3