New antidiabetic vanadyl-pyridone complexes: effect of equivalent transformation of coordinating atom in the ligand
New antidiabetic vanadyl-pyridone complexes: effect of equivalent transformation of coordinating atom in the ligand
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DOI：
10.1016/s0010-8545(03)00031-6
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发表时间：
2003-10-01
影响因子：
20.6
通讯作者：
Kiss, T
中科院分区：
文献类型：
--
作者：
Sakurai, H;Tamura, A;Kiss, T
为了治疗胰岛素依赖性 1 型和非胰岛素依赖性 2 型糖尿病，两种有效的抗糖尿病氧钒吡啶酮复合物，双（1-氧-2-吡啶硫醇）氧钒（IV），（VO（opt）（2））和双（1-氧-2-吡啶酮）氧钒（IV），（VO（opd）（2）），基于通过使用等效转化概念对糖尿病模型动物进行的结果，已被证明可以有效改变化合物的化学性质。通过使用血液循环监测-电子顺磁共振（BCM-EPR）检查了它们的理化性质、化学规格、离体大鼠脂肪细胞的体外胰岛素模拟活性、1型和2型糖尿病动物的体内抗糖尿病活性以及活体大鼠血流中氧钒物种的金属动力学特征。两种复合物均表现出比VOSO4更高的体外胰岛素模拟活性，并且VO(opt)(2)的活性优于VO(opd)(2)。然而，对 1 型糖尿病大鼠口服给药时，较低剂量的 VO(opd)(2) 比 VO(opt)(2) 更有效。结果得到化学规格和金属动力学（金属处置动力学）参数的支持。 (C) 2003 Elsevier B.V. 保留所有权利。
To treat both insulin-dependent type 1 and non-insulin-dependent type 2 diabetic mellitus, two potent antidiabetic vanadyl pyridone complexes, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), (VO(opt)(2)) and bis(1-oxy-2-pyridonato)oxovanadium(IV), (VO(opd)(2)), were proposed on the basis of the results of diabetic model animals by using a concept of equivalent transformation, which has been proved to be effective in changing the chemical property of a compound. Their physico-chemical properties, chemical specications, in vitro insulin-mimetic activity in isolated rat adipocytes, in vivo antidiabetic activity in both type 1 and type 2 diabetic animals, and metallokinetic feature of the vanadyl species in the blood flow of live rats by using blood circulation monitoring-electron paramagnetic resonance (BCM-EPR) were examined. Both complexes exhibited higher in vitro insulin-mimetic activity than VOSO4, and the activity of VO(opt)(2) was superior to that of VO(opd)(2). However, on oral administration to type 1 diabetic rats, VO(opd)(2) was more effective at lower dose than VO(opt)(2). The results are supported by chemical specifications and metallokinetic (kinetic of metal disposition) parameters. (C) 2003 Elsevier B.V. All rights reserved.