X-ray and molecular modelling studies of new potential aldose reductase inhibitors

Aldose Reductase Inhibitors as Potential Therapeutic Drugs of Diabetic Complications

Diabetes mellitus has become a major health threat as a global rise in it has been seen. The chronic disease has afflicted over 171 million people worldwide in 2000 and the incidence is expected to grow steadily to 366 million by 2030. As of May 2008, an estimated 92 million adults in China of the most populous country were living with diabetes and 148 million adults with prediabetes [1]. Diabe...

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...

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...

Current status of aldose reductase inhibitors.

Selective irreversible inhibitors of aldose reductase.

A series of 5-substituted-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid analogues have been examined as irreversible inhibitors of aldose reductase. The 5-alpha-bromoacetamide and 5-alpha-iodoacetamide analogues 5 and 6 gave irreversible inhibition of aldose reductase while the 5-alpha-chloroacetamide analogue 3 did not show this type of inhibition. Protection studies indicate that irreve...