New PPARgamma ligands based on barbituric acid: virtual screening, synthesis and receptor binding studies

Bioorg Med Chem Lett. 2008 Sep 15;18(18):4959-62. doi: 10.1016/j.bmcl.2008.08.028. Epub 2008 Aug 14.

Abstract

A new series of PPARgamma ligands based on barbituric acid (BA) has been designed employing virtual screening and molecular docking approach. To validate the computational approach, designed molecules were synthesized and evaluated in in vitro radioligand binding studies. Out of the total 14 molecules, 6 were found to bind to the murine PPARgamma with IC(50) ranging from 0.1 to 2.5 microM as compared to reference standard, pioglitazone (IC(50)=0.7 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Barbiturates / chemical synthesis*
  • Barbiturates / chemistry
  • Barbiturates / pharmacology*
  • Combinatorial Chemistry Techniques
  • Inhibitory Concentration 50
  • Ligands
  • Mice
  • Molecular Structure
  • PPAR gamma / agonists*
  • Pioglitazone
  • Structure-Activity Relationship
  • Thiazolidinediones / pharmacology

Substances

  • Barbiturates
  • Ligands
  • PPAR gamma
  • Thiazolidinediones
  • barbituric acid
  • Pioglitazone