title: Effects of structural and electronic characteristics of chalcones on the activation of peroxisome proliferator-activated receptor gamma.
abstract: Chalcones share some structural similarities with GW-1929, a highly-selective and potent agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). In this study, we tested 53 structurally diverse chalcones to identify characteristics essential for PPARγ activation in a GAL4-based transactivation assay. This screen identified several novel chalcone agonists of PPARγ. Our results indicate that chalcones with an electron rich group or sterically large groups such as naphthyl on the carbonyl side tend to activate PPARγ. The absence of any strict structural or electronic requirements suggests that the flexibility of the PPARγ ligand binding pocket may allow binding of diverse chalcones with some preference for a slightly larger electron-rich group on the carbonyl side. We predict that further structure-activity relationship studies on chalcones with naphthalene or electron-rich groups near the carbonyl moiety will lead to the development of more potent PPARγ agonists.
authors.affiliation: Department of Biological Science, California State University, Fullerton, CA 92831, USA.
authors.forename: Jason Taylor
authors.initials: JT
authors.lastname: Schott
authors.forename: Charles Edward
authors.initials: CE
authors.lastname: Mordaunt
authors.forename: Anthony Joseph
authors.initials: AJ
authors.lastname: Vargas
authors.forename: Martin Antonio
authors.initials: MA
authors.lastname: Leon
authors.forename: Kevin Hsinwen
authors.initials: KH
authors.lastname: Chen
authors.forename: Mandeep
authors.initials: M
authors.lastname: Singh
authors.forename: Mikiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Emilio Leal
authors.initials: EL
authors.lastname: Cardenas
authors.forename: Santanu
authors.initials: S
authors.lastname: Maitra
authors.forename: Nilay Vinod
authors.initials: NV
authors.lastname: Patel
authors.forename: Hubrecht Johan Peter
authors.initials: HJ
authors.lastname: de Lijser
mesh_terms: D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D047188:Chalcones; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D047495:PPAR gamma; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors