Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity.
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Choi J, Ko Y, Lee HS, Park YS, Yang Y, Yoon S
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.
- PubMed ID
- 19879669 [ View in PubMed]
- 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.
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- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Rosiglitazone Peroxisome proliferator-activated receptor gamma IC 50 (nM) 267 N/A N/A Details