Planta Med 2013; 79 - PC3
DOI: 10.1055/s-0033-1348559

Ligand Based Drug Design of Novel Aldose Reductase Inhibitors Based Off β-Glucogallin: A Major Active Component from E. officinalis, A Traditional Ayurvedic Botanical

L Li 1, KC Chang 2, J Ponder 1, Y Zhou 1, H Ali 1, A Adedoyin 1, B Shieh 1, JM Petrash 2, DV LaBarbera 1
  • 1Department of Pharmaceutical Sciences
  • 2Department of Ophthalmology; University of Colorado, Anschutz Medical Campus, Aurora, CO 80045

The plant Emblica officinalis has been used for thousands of years as an Indian Ayurvedic preparation to treat complications of diabetes, particularly diabetic eye disease. We have isolated and characterized β-glucogallin (BGG) from E. officinalis, as a potent and selective inhibitor (IC50= 17µM) of AKR1B1. Novel glycosides based on the BGG scaffold were designed, synthesized, and evaluated as stable aldose reductase inhibitors. Introducing new linkages between the sugar moiety and the gallate ring to replace the labile ester linkage identified derivatives that are compatible in activity with greatly improved stability. Identifying an effective and stable linkage is a key step in future structure based drug design based to develop novel, potent and specific therapeutics against diabetic eye disease.