Department of Pharmacy, University of Pisa, Pisa, Italy.
Department of Earth Sciences, University of Pisa, Pisa, Italy.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1194-1205. doi: 10.1080/14756366.2020.1763331.
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 -(arylmethyl)hydroxylamines. The synthesised compounds proved to be active against the target enzyme. The best performing inhibitor, compound ()- proved also to reduce both cell death and the apoptotic process when tested in an model of diabetic retinopathy made of photoreceptor-like 661w cell line exposed to high-glucose medium, counteracting oxidative stress triggered by hyperglycaemic conditions.
醛糖还原酶是长期糖尿病并发症发展的关键酶，其抑制作用为受这些病理影响的人群提供了一种可行的治疗方法。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。本文描述了一种新型氧肟酸衍生物的合成方法，该方法是通过 1,5-二羰基底物与-(芳基甲基)羟胺反应得到的。所合成的化合物对靶酶表现出活性。当在高葡萄糖培养基中暴露于高葡萄糖的光感受器样 661w 细胞系的糖尿病性视网膜病变模型中进行测试时，表现最佳的抑制剂化合物 ()- 还可以降低细胞死亡和凋亡过程，从而抵消高血糖条件下引发的氧化应激。
