Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase,Archiv der Pharmazie

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Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase
Archiv der Pharmazie ( IF 4.3 ) Pub Date : 2020-04-01 , DOI: 10.1002/ardp.201900371
Wanrong Huang ₁ , Yue Zhang ₁ , Xu Liang ₁ , Lichun Yang ₁

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In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2‐thioxothiazolidine‐4‐one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The experimental diabetes was induced by the intraperitoneal administration of streptozotocin in male Wistar rats. Compound 6e showed positive modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot analysis in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.

中文翻译：

取代的 2-thioxothiazolidin-4-one 衍生物通过抑制醛糖还原酶显示出对糖尿病性白内障的保护作用

为了开发一类新的针对糖尿病性白内障的强效醛糖还原酶抑制剂，通过简便的合成路线以优异的收率合成了一系列新型 2-thioxothiazolidine-4-one 衍生物。这些化合物针对醛 (ALR1) 和醛糖还原酶 (ALR2) 进行了测试，它们显示出相当大的抑制活性。在测试的衍生物中，化合物 6e 显示出对 ALR2 的选择性和优异的抑制作用，而不是 ALR1。实验性糖尿病是通过在雄性 Wistar 大鼠中腹腔注射链脲佐菌素诱导的。化合物 6e 在糖尿病大鼠中显示出对体重、血糖和血胰岛素水平的积极调节。正如在患有白内障的 Wistar 大鼠的晶状体匀浆中的蛋白质印迹分析所证明的那样，化合物 6e 也显示出 ALR2 抑制。

更新日期：2020-04-01

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