Development of Aldose Reductase Inhibitors for the Treatment of Inflammatory Disorders and Cancer: Current Drug Design Strategies and Future Directions

Abstract

Aldose Reductase (AR) is an enzyme that converts glucose to sorbitol during the polyol pathway of glucose metabolism. AR has been shown to be involved in the development of secondary diabetic complications due to its involvement in causing osmotic as well as oxidative stress. Various AR inhibitors have been tested for their use to treat secondary diabetic complications, such as retinopathy, neuropathy, and nephropathy in clinical studies. Recent studies also suggest the potential role of AR in mediating various inflammatory complications. Therefore, the studies on the development and potential use of AR inhibitors to treat inflammatory complications and cancer besides diabetes are currently on the rise. Further, genetic mutagenesis studies, computer modeling, and molecular dynamics studies have helped design novel and potent AR inhibitors. This review discussed the potential new therapeutic use of AR inhibitors in targeting inflammatory disorders and cancer besides diabetic complications. Further, we summarized studies on how AR inhibitors have been designed and developed for therapeutic purposes in the last few decades.