Abstract

Aldose reductase is a key enzyme in the development of long term diabetic complications and its inhibition represents a viable therapeutic solution for people affected by these pathologies. Therefore, the search for effective aldose reductase inhibitors is a timely and pressing challenge. Herein we describe the access to a novel class of oxyimino derivatives, obtained by reaction of a 1,5-dicarbonyl substrate with O-(arylmethyl)hydroxylamines. The synthesised compounds proved to be active against the target enzyme. The best performing inhibitor, compound (Z)-8, proved also to reduce both cell death and the apoptotic process when tested in an in vitro model of diabetic retinopathy made of photoreceptor-like 661w cell line exposed to high-glucose medium, counteracting oxidative stress triggered by hyperglycaemic conditions.

摘要

醛糖还原酶是长期糖尿病并发症发展中的关键酶，其抑制作用为受这些病理影响的人们提供了可行的治疗方案。因此，寻找有效的醛糖还原酶抑制剂是一个及时而紧迫的挑战。在本文中，我们描述了通过1，5-二羰基底物与O-（芳基甲基）羟胺反应获得的一类新型的氧亚氨基衍生物。已证明合成的化合物对目标酶具有活性。在体外测试中，性能最好的抑制剂化合物（Z）-8也被证明可以减少细胞死亡和凋亡过程 由暴露于高葡萄糖培养基的感光受体样661w细胞系制成的糖尿病性视网膜病变模型，可抵消高血糖条件引发的氧化应激。