Selectivity of 3'-O-methylponkoranol for inhibition of N- and C-terminal maltase glucoamylase and sucrase isomaltase, potential therapeutics for digestive disorders or their sequelae

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6491-4. doi: 10.1016/j.bmcl.2011.08.069. Epub 2011 Aug 22.

Abstract

Human maltase glucoamylase (MGAM) and sucrase isomaltase (SI) are two human intestinal glucosidases responsible for the final step of starch hydrolysis. MGAM and SI are anchored to the small intestinal brush border epithelial cells and contain two catalytic N-terminal and C-terminal subunits. In this study, we report the inhibition profile of 3'-O-methylponkoranol for the individual recombinant N and C terminal enzymes and compare the inhibitory activities of this compound with de-O-sulfonated ponkoranol. We show that 3'-O-methylponkoranol inhibits the different subunits to different extents, with extraordinary selectivity for C-terminal SI (K(i)=7±2nM). The enzymes themselves could serve as therapeutic targets for the treatment of digestive disorders or their sequelae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amylopectin / chemistry
  • Amylose / chemistry
  • Carbohydrate Sequence
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Gastrointestinal Diseases / drug therapy*
  • Glycoside Hydrolase Inhibitors*
  • Humans
  • Molecular Sequence Data
  • Sucrase-Isomaltase Complex / antagonists & inhibitors*
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use

Substances

  • 3'-O-methylponkoranol
  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Thiophenes
  • Amylose
  • Amylopectin
  • Sucrase-Isomaltase Complex