Development of Novel Indole-Based Bifunctional Aldose Reductase Inhibitors/Antioxidants as Promising Drugs for the Treatment of Diabetic Complications

The document details the development of new indole-based compounds that act as both aldose reductase inhibitors (ARIs) and antioxidants, which are promising for the treatment of diabetic complications. It reports on the antiradical and antioxidant activities of these compounds, with cemtirestat (5a) showing superior antiradical activity compared to standard antioxidants and effectively preventing lipid peroxidation and protecting red blood cells from oxidative damage. The study also assessed the inhibitory effects on sorbitol accumulation in rat eye lenses and the sciatic nerve of diabetic rats, with compounds 3d, 3f, and 7a demonstrating strong inhibition and compound 5a showing high efficacy in vivo, with about 20% inhibition of sorbitol accumulation in the sciatic nerve of diabetic rats. The document concludes that these multi-target directed drugs, especially cemtirestat (5a), could be beneficial for diabetic complications due to their dual functions and favorable properties, with 5a currently in preclinical evaluation. The number of subjects involved in the study is not specified.