Imamura Y, Migita T, Uriu Y, Otagiri M, Okawara T
Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi, Kumamoto 862-0973, Japan.
J Biochem. 2000 Apr;127(4):653-8. doi: 10.1093/oxfordjournals.jbchem.a022653.
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.
以4-苯甲酰吡啶（4BP）为底物，研究了黄酮类化合物（高良姜素、山奈酚、槲皮素、杨梅素、桑色素和紫杉叶素）对兔心脏羰基还原酶（RHCR）的抑制作用。发现黄酮类化合物的立体化学特征是决定其对RHCR抑制效力的一个因素。此外，黄酮类化合物的亲脂性以及清除或抗氧化作用可能会使其对RHCR抑制作用的构效关系变得复杂。槲皮素对NADPH呈非竞争性抑制，对4BP呈竞争性抑制，这表明它在RHCR的底物结合位点与4BP竞争。RHCR能有效还原苯醌（1,4-苯醌和2-甲基-1,4-苯醌）和萘醌（1,4-萘醌和甲萘醌）。当以甲萘醌为底物时，高良姜素是RHCR的有效抑制剂，并在有RHCR、NADPH和甲萘醌存在的情况下阻止超氧阴离子自由基的形成。黄酮类化合物可能是通过抑制RHCR来抑制醌类心脏毒性的有用化合物。
