| Title | Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity. | | Author(s) | Choi J, Ko Y, Lee HS, Park YS, Yang Y, Yoon S | | Institution | Sookmyung Women's University, Department of Biological Sciences, Research Center for Women's Diseases, Hyochangwongil 52, Yongsan-gu, Seoul 140-742, Republic of Korea. | | Source | Eur J Med Chem 2009 Oct 2. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19879669 |
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