Functional compounds with antioxidant and AR inhibitory activities have been recognized as an important strategy in the prevention and treatment of diabetic complications, and the search for tyrosinase inhibitors is important for the treatment of hyperpigmentation, development of skin-whitening agents, and use as preservatives in the food industry.
Several ALR2 inhibitors with a promising pre-clinical ability to address diabetic complications and inflammatory diseases are being developed during the observed timeframe.
This work represents a promising matrix for developing new potential therapeutic candidates for prevention of diabetic complications through targeting aldose reductase enzyme.[Formula: see text].
The study stands out as a systematic attempt to generate aldose reductase differential inhibitors (ARDIs) intended to target long-term diabetic complications while leaving unaltered the detoxifying role of the enzyme.
Since aldose reductase is the first and ratelimiting enzyme of the polyol pathway, it is predicted that restriction fragment length polymorphisms at the aldose reductase gene locus may influence catalytic activity and determine individual susceptibility to the diabetic complications.
These results suggest that NO may be an endogenous regulator of aldose reductase, and consequently the polyol pathway of glucose metabolism; which has been implicated in the pathogenesis of secondary diabetic complications.
The result should facilitate refined structural analysis and the development of new specific aldose reductase inhibitors for the treatment of diabetic complications.
Aldose reductase (ALR2) has been the target of therapeutic intervention for over 40 years; first, for its role in long-term diabetic complications and more recently as a key mediator in inflammation and cancer.
The formation of advanced glycation end-products (AGE) and aldose reductase activity have been implicated in the development of diabetic complications.
There are 15 human AKRs of these AKR1B1, AKR1C1-1C3, AKR1D1, and AKR1B10 have been implicated in diabetic complications, steroid hormone dependent malignancies, bile acid deficiency and defects in retinoic acid signaling, respectively.