Oxy-imino saccharidic derivatives as a new structural class of aldose reductase inhibitors endowed with anti-oxidant activity

Aldose reductase is a key enzyme in the development of long term diabetic complications and its inhib-ition represents a viable therapeutic solution for people affected by these pathologies. Therefore, thesearch for effective aldose reductase inhibitors is a timely and pressing challenge. Herein we describe theaccess to a novel class of oxyimino derivatives, obtained by reaction of a 1,5-dicarbonyl substrate withO-(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 apoptoticprocess when tested in anin vitromodel of diabetic retinopathy made of photoreceptor-like 661w cellline exposed to high-glucose medium, counteracting oxidative stress triggered by hypergly-caemic conditions.