Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Département Médicaments et Technologies pour la Santé (DMTS), Université Paris Saclay, Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA), Institut National de Recherche pour l'Agricolture, l'Alimentation et l'Environment (INRAE), SIMoS, 91191 Gif-sur-Yvette, France.
Biomolecules. 2022 Mar 14;12(3):448. doi: 10.3390/biom12030448.
Aldose reductase (ALR2) is the enzyme in charge of developing cellular toxicity caused by diabetic hyperglycemia, which in turn leads to the generation of reactive oxygen species triggering oxidative stress. Therefore, inhibiting ALR2 while pursuing a concomitant anti-oxidant activity through dual-acting agents is now recognized as the gold standard treatment for preventing or at least delaying the progression of diabetic complications. Herein we describe a novel series of ()-benzaldehyde -benzyl oximes , , , and as ALR2 inhibitors endowed with anti-oxidant properties. Inspired by the natural products, the synthesized derivatives are characterized by a different polyhydroxy substitution pattern on their benzaldehyde fragment, which proved crucial for both the enzyme inhibitory activity and the anti-oxidant capacity. Derivatives ()-2,3,4-trihydroxybenzaldehyde -(3-methoxybenzyl) oxime () and ()-2,3,4-trihydroxybenzaldehyde -(4-methoxybenzyl) oxime () turned out to be the most effective dual-acting products, proving to combine the best ALR2 inhibitory properties with significant anti-oxidant efficacy.
醛糖还原酶（ALR2）是负责引发糖尿病高血糖引起的细胞毒性的酶，这反过来又导致活性氧的产生，引发氧化应激。因此，通过双作用剂抑制 ALR2 同时追求伴随的抗氧化活性，现在被认为是预防或至少延迟糖尿病并发症进展的金标准治疗方法。在这里，我们描述了一系列新型（）-苯甲醛-苄基肟，，，和作为具有抗氧化特性的 ALR2 抑制剂。受天然产物的启发，合成的衍生物在其苯甲醛片段上具有不同的多羟基取代模式，这对酶抑制活性和抗氧化能力都至关重要。衍生物（）-2,3,4-三羟基苯甲醛-（3-甲氧基苄基）肟（）和（）-2,3,4-三羟基苯甲醛-（4-甲氧基苄基）肟（）被证明是最有效的双重作用产物，它们将 ALR2 抑制特性与显著的抗氧化功效结合在一起。
