Chen S, Hwang J, Deng P S
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010.
Arch Biochem Biophys. 1993 Apr;302(1):72-7. doi: 10.1006/abbi.1993.1182.
A structure-activity study was carried out to determine the important regions of baicalein and oroxylin A, two flavones isolated from the Chinese herb Scutellariae 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.
开展了一项构效关系研究，以确定从中药黄芩中分离出的两种黄酮——黄芩素和木犀草素A，在抑制NAD(P)H：醌受体氧化还原酶（EC 1.6.99.2；DT-黄递酶）方面的重要区域。这种醌还原酶是一种维生素K还原酶。它是研究口服抗凝剂作用模式的一个靶点，并已被用作模型酶。发现这两种黄酮在纳摩尔范围内抑制这种醌还原酶。发现这些黄酮的5-羟基、7-羟基、8-羟基和2-苯基对于它们对该酶的抑制作用很重要。这些黄酮对该酶的NADH-甲萘醌还原酶活性、NADH-铁氰化钾还原酶活性和NADH-甲基红还原酶活性的抑制谱不同。因此，尽管发现这些黄酮是NADH的竞争性抑制剂，但它们可能不是通过与烟酰胺核苷酸结合位点结合来抑制该酶的。进行了抑制动力学研究，结果表明这些化合物与双香豆素和苯茚二酮的结合位点不同。这些结果表明，这些黄酮是NAD(P)H：醌受体氧化还原酶的一种新型抑制剂，有可能用作抗凝药物。
