Oxy-imino saccharidic derivatives as a new structural class of aldose reductase inhibitors endowed with anti-oxidant activity. (1st January 2020)

• Record Type: Journal Article
• Authors: D'Andrea, Felicia; Sartini, Stefania; Piano, Ilaria; Franceschi, Matteo; Quattrini, Luca; Guazzelli, Lorenzo; Ciccone, Lidia; Orlandini, Elisabetta; Gargini, Claudia; La Motta, Concettina; Nencetti, Susanna
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 1194
• Page End: 1205
• Publication Date: 2020-01-01
• Subjects: Diabetes -- aldose reductase inhibitors -- aldohexos-5-uloses -- oxy-imino saccharidic derivatives -- azapyranose; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1763331
• Languages: English
• ISSNs: 1475-6366

Abstract

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.