title: Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity.
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.
authors.affiliation: Sookmyung Women's University, Department of Biological Sciences, Research Center for Women's Diseases, Hyochangwongil 52, Yongsan-gu, Seoul 140-742, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Choi
authors.forename: Yoonae
authors.initials: Y
authors.lastname: Ko
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Yun Sun
authors.initials: YS
authors.lastname: Park
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Sukjoon
authors.initials: S
authors.lastname: Yoon
mesh_terms: D002460:Cell Line; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D047495:PPAR gamma; D012236:Rhodanine