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 2-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 lead therapeutic toward the treatment of diabetic eye disease.

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells

“…BGG (Fig. 2) is a novel ARI isolated from Indian gooseberry fruits ( Emblica officinalis ), which we previously demonstrated to have ARI activity in vitro and in a lens culture system [27, 32]. BGG significantly prevented cell loss (Fig.…”

“…BGG was obtained as previously reported [32]. Sorbinil was generously provided by Pfizer Central Research (Groton, CT, USA).…”

“…β-glucogallin (BGG), a novel ARI isolated from Indian gooseberry ( Emblica officinalis ) [31], inhibits AR activity in cells and ocular tissues [27, 32]. Lens culture in HG condition demonstrated the inhibitory activity of BGG as evidenced by decreased accumulation of sorbitol [31], an inducer of osmotic stress associated with diabetic cataract development [33].…”

Characterization of Emodin as a Therapeutic Agent for Diabetic Cataract

“…AKR activity was determined spectrophotometrically by measuring the decrease in absorbance at 340 nm upon oxidation of NADPH. 42 Reaction mixtures in 1.0 mL quartz cuvettes contained DL-glyceraldehyde (1.0 mM for AKR1B1, 25 mM for AKR1B10, and 15 mM for AKR1A1) and 150 μ M NADPH in KAB buffer (50 mM HEPES, pH 7.5, 150 mM NaCl, 1 mM DTT, 10 mM MgCl 2 ). For kinetics studies, rates were measured in triplicate under varying substrate and inhibitors (emodin and chrysophanol) concentrations.…”

Photocatalytic synthesis of anilides from nitrobenzenes under visible light irradiation: 2 in 1 reaction

“…Anilide and its derivatives occupy pivotal positions in organic synthesis and synthesis of biologically and pharmaceutically active compounds [1][2][3][4]. Generally, the amides are produced through the reaction of a carboxylic acid or ester with an amine.…”