Pyranocoumarins: a new class of anti-hyperglycemic and anti-dyslipidemic agents

Bioorg Med Chem Lett. 2009 Nov 15;19(22):6447-51. doi: 10.1016/j.bmcl.2009.09.031. Epub 2009 Sep 12.

Abstract

A series of pyranocoumarin derivatives were synthesized and evaluated in vivo for their anti-hyperglycemic as well as anti-dyslipidemic activities. Compounds 7a, 7c, 8a, 8b, 8c, 8e and 8f have shown promising anti-hyperglycemic activities in sucrose loaded model (SLM) as well as sucrose challenged streptozotocin induced diabetic rat model (STZ). Compounds 8a and 8b were showing 38.0% and 42.0% blood glucose lowering activity in db/db mice model. In vitro anti-hyperglycemic activity evaluation exhibited that compounds 8a (IC(50)=24.5 microM) and 8b (IC(50)=36.2 microM) are potential PTP-1B inhibitors thereby revealing their possible mechanism of anti-diabetic action. Compounds 7a, 7b, 8a, 8b, 8d, 8e and 8f have shown significant anti-dyslipidemic activity in triton induced dyslipidemia in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Hypoglycemic Agents / classification
  • Hypoglycemic Agents / therapeutic use
  • Lipid Metabolism / drug effects
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism
  • Pyranocoumarins / metabolism
  • Pyranocoumarins / therapeutic use*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • PPAR gamma
  • Pyranocoumarins