Preliminary evaluation of rat kidney aldose reductase inhibitory activity of 2-phenylindole derivatives: affiliation to antioxidant activity

Diabetic complications including nephropathy, neuropathy, and cataract are leading causes of end-stage renal diseases and neurological disorders. Aldose reductase (AR), the rate-limiting enzyme of the polyol pathway, catalyzes the reduction of glucose to sorbitol via NADPH. Excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. Indole ring-containing AR inhibitors have received considerable attention as potential treatments for diabetic complications. However, these agents have not achieved worldwide use because of limited efficacy or unacceptable adverse effects. In this study, a series of 2-phenylindole derivatives were evaluated via an in vitro spectrophotometric assay for their ability to inhibit rat kidney AR. In addition, the antioxidant and AR inhibitory activities of the compounds under study were compared.