title: Design of an amide N-glycoside derivative of β-glucogallin: a stable, potent, and specific inhibitor of aldose reductase.
abstract: β-Glucogallin (BGG), a major component of the Emblica officinalis medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). New linkages (ether/triazole/amide) were introduced via high yielding, efficient syntheses to replace the labile ester, and an original two-step (90%) preparation of BGG was developed. Inhibition of AKR1B1was assessed in vitro and using transgenic lens organ cultures, which identified the amide linked glucoside (BGA) as a stable, potent, and selective therapeutic lead toward the treatment of diabetic eye disease.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Science, University of Colorado Anschutz Medical Campus , Aurora, Colorado 80045, United States.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Li
authors.forename: Kun-Che
authors.initials: KC
authors.lastname: Chang
authors.forename: Yaming
authors.initials: Y
authors.lastname: Zhou
authors.forename: Biehuoy
authors.initials: B
authors.lastname: Shieh
authors.forename: Jessica
authors.initials: J
authors.lastname: Ponder
authors.forename: Adedoyin D
authors.initials: AD
authors.lastname: Abraham
authors.forename: Hadi
authors.initials: H
authors.lastname: Ali
authors.forename: Anson
authors.initials: A
authors.lastname: Snow
authors.forename: J Mark
authors.initials: JM
authors.lastname: Petrash
authors.forename: Daniel V
authors.initials: DV
authors.lastname: LaBarbera
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006027:Glycosides; D047348:Hydrolyzable Tannins; C060474:glucogallin; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase