Dual action spirobicycloimidazolidine-2,4-diones: antidiabetic agents and inhibitors of aldose reductase-an enzyme involved in diabetic complications

Bioorg Med Chem Lett. 2013 Jan 15;23(2):488-91. doi: 10.1016/j.bmcl.2012.11.039. Epub 2012 Nov 24.

Abstract

The desired 3-(arylsulfonyl)spiroimidazolidine-2,4-diones were synthesized by reacting spiroiminoimidazolidine-2,4-dione with arylsulfonyl chlorides. Spiroimidazolidine-2,4-dione was in turn synthesized from norcamphor. Structures of the synthesized molecules were established by modern spectroscopic techniques. The synthesized compounds were screened for in vivo antidiabetic activity and aldose reductase inhibition. Compounds 2a, 2b and 2g exhibited excellent dual activity, compound 2a being most prominent. These results reveal that the synthesized compounds may serve as the molecule of choice to treat diabetes and diabetic complications using a single medication.

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Animals
  • Blood Glucose / analysis
  • Diabetes Complications / enzymology*
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus, Experimental
  • Enzyme Activation / drug effects
  • Humans
  • Hydantoins / chemical synthesis*
  • Hydantoins / chemistry
  • Hydantoins / pharmacology
  • Hypoglycemic Agents / chemical synthesis*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Inhibitory Concentration 50

Substances

  • Blood Glucose
  • Hydantoins
  • Hypoglycemic Agents
  • Aldehyde Reductase