Daş-Evcimen Net, Bozdağ-Dündar Oya, Sarikaya Mutlu, Ertan Rahmiye
Department of Biochemistry, Faculty of Pharmacy, Ankara University.
J Enzyme Inhib Med Chem. 2008 Jun;23(3):297-301. doi: 10.1080/14756360701475282.
Aldose reductase (AR) is implicated to play a critical role in diabetes and cardiovascular complications because of the reaction it catalyzes. AR enzyme appears to be the key factor in the reduction of glucose to sorbitol. Synthesis and accumulation of sorbitol in cells due to AR activity is the main cause of diabetic complications, such as diabetic cataract, retinopathy, neuropathy and nephropathy. Aldose reductase inhibitors have been found to prevent sorbitol accumulation in tissues. Numerous compounds have been prepared in order to improve the pharmacological prophile of inhibition of aldose reductase enzyme. In this study, seventeen flavonyl-2,4-thiazolidinediones (flavonyl-2,4-TZD) (Ia-e, IIa-e and IIIa-g) were tested for their ability to inhibit rat kidney AR. Compound Ib showed the highest inhibitory activity (88.69 +/- 1.46%) whereas Ia, IIa, IIIa, IIIb also showed significant inhibitory activity (49.26 +/- 2.85, 67.29 +/- 1.09, 71.11 +/- 1.95, 64.86 +/- 1.21%, respectively).
醛糖还原酶（AR）因其催化的反应而被认为在糖尿病和心血管并发症中起关键作用。AR酶似乎是葡萄糖还原为山梨醇的关键因素。由于AR活性导致细胞中山梨醇的合成和积累是糖尿病并发症的主要原因，如糖尿病性白内障、视网膜病变、神经病变和肾病。已发现醛糖还原酶抑制剂可防止组织中山梨醇的积累。为了改善抑制醛糖还原酶的药理学特性，人们制备了许多化合物。在本研究中，测试了十七种黄酮基-2,4-噻唑烷二酮（黄酮基-2,4-TZD）（Ia-e、IIa-e和IIIa-g）抑制大鼠肾脏AR的能力。化合物Ib表现出最高的抑制活性（88.69 +/- 1.46%），而Ia、IIa、IIIa、IIIb也表现出显著的抑制活性（分别为49.26 +/- 2.85、67.29 +/- 1.09、71.11 +/- 1.95、64.86 +/- 1.21%）。
