Isolation, structure identification and SAR studies on thiosugar sulfonium salts, neosalaprinol and neoponkoranol, as potent α-glucosidase inhibitors

Bioorg Med Chem. 2011 Mar 15;19(6):2015-22. doi: 10.1016/j.bmc.2011.01.052. Epub 2011 Jan 31.

Abstract

Two hitherto missing members of sulfonium salts family in Salacia genus plants as a new class of α-glucosidase inhibitors, neoponkoranol (7) and neosalaprinol (8), were isolated from the water extracts, and their structures were unambiguously identified. For further SAR studies on this series of sulfonium salts, several epimers of 7 and 8 were synthesized, and their inhibitory activities against rat small intestinal α-glucosidases were evaluated. Among them, 3'-epimer of 7 was found most potent in this class of molecules, and revealed as potent as currently used antidiabetics, voglibose and acarbose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Glycoside Hydrolase Inhibitors*
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology
  • Rats
  • Salacia / chemistry
  • Structure-Activity Relationship
  • Sugar Alcohols / chemistry*
  • Sugar Alcohols / isolation & purification
  • Sugar Alcohols / pharmacology
  • Thiophenes / chemistry*
  • Thiophenes / isolation & purification
  • Thiophenes / pharmacology
  • Thiosugars / chemistry*
  • Thiosugars / isolation & purification
  • Thiosugars / pharmacology
  • alpha-Glucosidases / metabolism

Substances

  • 1,4-dideoxy-1,4-((2,3,4,5,6-pentahydroxyhexyl)episulfoniumylidene)arabinitol
  • 1,4-dideoxy-1,4-((2,3-dihydroxypropyl)episulfoniumylidene)arabinitol
  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Sugar Alcohols
  • Thiophenes
  • Thiosugars
  • alpha-Glucosidases