Inhibitory effects of flavonoids on rabbit heart carbonyl reductase.
The inhibitory effects of flavonoids (galangin, kaempferol, quercetin, myricetin, morin, and taxifolin) on rabbit heart carbonyl reductase (RHCR) were investigated using 4-benzoylpyridine (4BP) as the substrate. The stereochemical characteristics of the flavonoids were found to be a factor determining their inhibitory potencies toward RHCR. Furthermore, the lipophilicity, and the scavenging or antioxidative effects of the flavonoids were likely to complicate the structure-activity relationship of their inhibitory effects on RHCR. Quercetin inhibited RHCR uncompetitively with respect to NADPH and competitively with respect to 4BP, suggesting that it competes with 4BP at the substrate-binding site of RHCR. RHCR efficiently reduced benzoquinones (1,4-benzoquinone and 2-methyl-1, 4-benzoquinone) and naphthoquinones (1,4-naphthoquinone and menadione). Galangin was a potent inhibitor of RHCR when menadione was used as the substrate, and prevented the formation of the superoxide anion radical in the presence of RHCR, NADPH, and menadione. Flavonoids may be useful compounds for suppressing the cardiotoxicity of quinones by inhibiting RHCR.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto 862-0973, Japan. yorishig@gpo.kumamoto-u.ac.jp
Migita
T
T
Uriu
Y
Y
Otagiri
M
M
Okawara
T
T
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D011809:Quinones / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism
D000975:Antioxidants; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011725:Pyridines; D011809:Quinones; D013481:Superoxides; D014812:Vitamin K; C037032:galangin; C066738:4-benzoylpyridine; D009249:NADP; D011794:Quercetin; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase