Format

Send to

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

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

Author information

1
Sookmyung Women's University, Department of Biological Sciences, Research Center for Women's Diseases, Hyochangwongil 52, Yongsan-gu, Seoul 140-742, Republic of Korea.

Abstract

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.

PMID:
19879669
DOI:
10.1016/j.ejmech.2009.09.042
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center