Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity

Eur J Med Chem. 2010 Jan;45(1):193-202. doi: 10.1016/j.ejmech.2009.09.042. Epub 2009 Oct 2.


We applied an improved virtual screening scheme combining ligand-centric and receptor-centric methods for the identification of a new series of PPARgamma agonists known as (beta-carboxyethyl)-rhodanine derivatives which include a thiazolidin-based core structure, 2-thioxo-thiazolidine-4-one. An in vitro assay confirmed the nanomolar binding affinity in one of the (beta-carboxyethyl)-rhodanine derivatives, SP1818. It showed a PPARgamma agonistic activity similar to that of a known PPARgamma drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure-activity relationships of the rhodanine derivatives were investigated through comparative molecular field analysis. We also characterized the inconsistency between the in vitro binding affinity and cell-based transactivation ability by using a set of property-based molecular descriptors. The binding mode analysis provided new insight concerning their agonistic effect on PPARgamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Computer Simulation
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Models, Molecular
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / chemistry
  • PPAR gamma / metabolism
  • Protein Conformation
  • Rhodanine / analogs & derivatives*
  • Rhodanine / chemistry
  • Rhodanine / metabolism
  • Rhodanine / pharmacology*
  • Structure-Activity Relationship
  • User-Computer Interface


  • Ligands
  • PPAR gamma
  • Rhodanine