Molecular Modeling and Structure-based Drug Discovery Studies of Aldose Reductase Inhibitors

Molecular Modeling and Structure-based Drug Discovery Studies of Aldose Reductase Inhibitors

Aldose reductase has been implicated in the etiology of diabetic complications. A variety of compounds have been observed to inhibit aldose reductase and effective, orally active inhibitors of the enzyme have been investigated for many years. Although several of these compounds have progressed to the clinical level, only one such drug is currently on the market. Due to the limited number of ava...

A neural networks-based drug discovery approach and its application for designing aldose reductase inhibitors.

A novel approach that combines neural networks, computer docking and quantum mechanical method is developed to design potent aldose reductase inhibitors (ARIs). Neural networks is employed to determine the quantitative structure-activity relationship (QSAR) among the known ARIs. The physical descriptors of the neural networks, such as electronegativity and molar volume, are evaluated with first...

Synthesis, activity, and molecular modeling studies of novel human aldose reductase inhibitors based on a marine natural product.

Aldose reductase (ALR2) has been implicated in the etiology of diabetic complications, including blindness. Because of the limited number of currently available drugs for the prevention of these long-term complications, the discovery of new ALR2 inhibitors appears highly desirable. In this study, a polybrominated diphenyl ether (1) naturally occurring in a marine sponge was found to inhibit rec...

Structure-based enzyme inhibition mechanism studies of kaempferol and its prenylated derivatives as aldose reductase inhibitors using kinetics and molecular docking modeling

Activators and inhibitors of lens aldose reductase.

Aldose reductase in a highly purified state is unstable. It requires the presence of thiol groups to maintain it in an active form. The enzyme apparently exists in 3 forms, only one of which is active. Tetramethylene glutaric acid (TMG) is an effective aldose reductase inhibitor. However, a relatively high level of TMG is needed to depress dulcitol synthesis in the lens incubated in a galactose...