INHIBITION OF NAD(P)H-QUINONE ACCEPTOR OXIDOREDUCTASE BY FLAVONES - A STRUCTURE ACTIVITY STUDY
INHIBITION OF NAD(P)H-QUINONE ACCEPTOR OXIDOREDUCTASE BY FLAVONES - A STRUCTURE ACTIVITY STUDY
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DOI：
10.1006/abbi.1993.1182
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发表时间：
1993-04-01
影响因子：
3.9
通讯作者：
DENG, PSK
中科院分区：
文献类型：
--
作者：
CHEN, S;HWANG, J;DENG, PSK
对黄芩中黄芩素和芫花素A抑制NAD(P)H：醌受体氧化还原酶（EC 1.6.99.2; DT-diaphorase）的重要区域进行了结构活性研究。这种醌还原酶是维生素K还原酶。它是口服抗凝剂的靶点，并已被用作模型酶来研究其作用方式。发现这两种黄酮在纳摩尔范围内抑制醌还原酶。这些黄酮的5-羟基、7-羟基、8-羟基和2-苯基对酶的抑制作用很重要。不同黄酮对nadh -甲萘二酮还原酶活性、nadh -铁氰化钾还原酶活性和nadh -甲基红还原酶活性的抑制情况不同。因此，尽管黄酮被发现是NADH的竞争性抑制剂，但它们可能不会通过与烟酰胺核苷酸结合位点结合来抑制NADH。抑制动力学研究表明，这些化合物的结合位点不同于二香豆酚和苯茚酮。这些结果表明，这些黄酮是一种新型的NAD(P)H：醌受体氧化还原酶抑制剂，具有潜在的抗凝血作用。
A structure-activity study was carried out to determine the important regions of baicalein and oroxylin A, two flavones isolated from the Chinese herbScutellariae radix, in inhibiting NAD(P)H:quinone acceptor oxidoreductase (EC 1.6.99.2; DT-diaphorase). This quinone reductase is a vitamin K reductase. It is a target for and has been used as a model enzyme to investigate the mode of action of oral anticoagulants. The two flavones were found to inhibit this quinone reductase in nanomolar ranges. The 5-hydroxyl, 7-hydroxyl, 8-hydroxyl, and 2-phenyl groups of these flavones were found to be important for their inhibition of the enzyme. The inhibition profiles of the flavones on the NADH-menadione reductase activity, the NADH-potassium ferricyanide reductase activity, and the NADH-methyl red reductase activity of this enzyme were different. Therefore, even though the flavones were found to be competitive inhibitors with respect to NADH, they probably did not inhibit the enzyme by binding to the nicotinamide nucleotide binding site. Inhibition kinetic studies which indicated that these compounds bound to different sites than those for dicoumarol and phenindone were performed. These results indicate that these flavones are a new type of inhibitor of NAD(P)H:quinone acceptor oxidoreductase and potentially useful as anticoagulant drugs.