Amplification of the inhibitory activity and reversal of the selectivity of miglitol by C(2')-monofluorination

Arch Pharm (Weinheim). 2010 Oct;343(10):583-9. doi: 10.1002/ardp.200900256.

Abstract

Selective monofluorination of the α-glycosidase inhibitor and antidiabetic agent miglitol at positions C(2') or C(6) creates competitive inhibitors of glycosidases. Introducing a fluorine substituent at position C(6) results in a reduced binding to the enzyme whereas fluorination at C(2') produces an inhibitor with an activity four times higher than the parent compound. This compound is selective for the α-galactosidase from green coffee beans. Its screening against a panel of human cell lines showed a low cytotoxicity, therefore, making this compound an interesting candidate for further clinical investigations.

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / metabolism
  • 1-Deoxynojirimycin / pharmacology
  • Cell Line
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Halogenation
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Structure-Activity Relationship
  • alpha-Galactosidase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • miglitol
  • 1-Deoxynojirimycin
  • alpha-Galactosidase