Details

Autor(en) / Beteiligte

• Sim, Lyann
• Jayakanthan, Kumarasamy
• Mohan, Sankar
• Nasi, Ravindranath
• Johnston, Blair D
• Pinto, B. Mario
• Rose, David R

Titel

New Glucosidase Inhibitors from an Ayurvedic Herbal Treatment for Type 2 Diabetes: Structures and Inhibition of Human Intestinal Maltase-Glucoamylase with Compounds from Salacia reticulata

Ist Teil von

• Biochemistry (Easton), 2010-01, Vol.49 (3), p.443-451

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target α-amylases and intestinal glucosidases using α-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of α-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K i = 0.03 μM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates.