Sheu S Y, Chiang H C
School of Pharmacy, Taipei Medical College, Taiwan, R.O.C.
Anticancer Res. 1996 Jan-Feb;16(1):311-5.
Several plant hormones and analogues were tested for their inhibitory effects on xanthine oxidase. The flavoprotein enzyme, xanthine oxidase, catalyses the oxidation of hypoxanthine to xanthine and then xanthine to uric acid which has lambda max 295 nm. Uric acid was thus the basis for a spectrophotometric assay of the activity of xanthine oxidase. The results showed that trans-zeatin displayed the strongest activity (IC50 = 23.5 muM) on xanthine oxidase inhibition, followed by indole-3-acrylic acid (IC50 = 136.0 muM) and then by the mixed isomers of zeatin (trans-zeatin and cis-zeatin) (IC50 = 198.65 muM). Trans-zeatin induced an uncompetitive inhibition of the enzyme with respect to the substrate xanthine and the apparent inhibition constant (Ki) was 5.09 muM. However, zeatin riboside was inactive. Since xanthine oxidase serum levels are increased in hepatitis, mild hepatic intoxication, tumours brain tissues, and DNA damage induced by cytotoxic agents, it is expected that trans-zeatin may be useful for the treatment of these diseases as well as gout which is caused by deposition of uric acid in the joints and oxidative damage of tissue caused by generation of superoxide anion radical.
测试了几种植物激素及其类似物对黄嘌呤氧化酶的抑制作用。黄素蛋白酶黄嘌呤氧化酶催化次黄嘌呤氧化为黄嘌呤，然后黄嘌呤氧化为尿酸，尿酸的最大吸收波长为295nm。因此，尿酸是黄嘌呤氧化酶活性分光光度测定法的基础。结果表明，反式玉米素对黄嘌呤氧化酶抑制表现出最强活性（IC50 = 23.5μM），其次是吲哚 - 3 - 丙烯酸（IC50 = 136.0μM），然后是玉米素的混合异构体（反式玉米素和顺式玉米素）（IC50 = 198.65μM）。反式玉米素对底物黄嘌呤诱导了该酶的非竞争性抑制，表观抑制常数（Ki）为5.09μM。然而，玉米素核苷无活性。由于在肝炎、轻度肝中毒、肿瘤脑组织以及细胞毒性剂诱导的DNA损伤中黄嘌呤氧化酶血清水平会升高，预计反式玉米素可能对这些疾病以及痛风的治疗有用，痛风是由尿酸在关节中的沉积以及超氧阴离子自由基产生导致的组织氧化损伤引起的。
