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

Biochemistry. 2010 Jan 26;49(3):443-51. doi: 10.1021/bi9016457.


An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-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 alpha-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 microM), 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acarbose / chemistry
  • Binding Sites
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors*
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacology
  • Kinetics
  • Medicine, Ayurvedic
  • Plant Extracts / chemistry
  • Salacia / chemistry*
  • Structure-Activity Relationship
  • Sugar Alcohols / chemistry
  • Sulfates / chemistry
  • alpha-Glucosidases / chemistry*
  • alpha-Glucosidases / metabolism


  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Plant Extracts
  • Sugar Alcohols
  • Sulfates
  • salacinol
  • alpha-Glucosidases
  • Acarbose