Title:Development of Aldose Reductase Inhibitors for the Treatment of Inflammatory Disorders and Cancer: Current Drug Design Strategies and Future Directions
Volume: 28
Issue: 19
Author(s): Himangshu Sonowal and Kota V. Ramana*
Affiliation:
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555,United States
Keywords:
Aldose reductase, aldose reductase inhibitors, diabetes, drug discovery, inflammation, cancer.
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.