title: Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα.
abstract: The identification of novel PPAR ligands represents an attractive research to fully understand the complex biological pathways regulated by these receptors. Selective PPAR modulators, inverse agonists and antagonists of three PPAR isoforms could help to clarify biological effects on lipid and glucose homeostasis. Here we describe the identification of a group of N-(methylsulfonyl)amides, derived from PPARα agonist carboxylic acids. Transactivation and FRET assay confirmed an antagonist behaviour on PPARα for some of these compounds, with submicromolar IC(50). A preliminary analysis on selectivity α/γ revealed different profiles of inhibition or activation.
authors.affiliation: Dipartimento di Farmacia, Università G. d'Annunzio, via dei Vestini, Chieti 66100, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ammazzalorso
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Antonella
authors.initials: A
authors.lastname: Giancristofaro
authors.forename: Barbara
authors.initials: B
authors.lastname: De Filippis
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Matteo
authors.forename: Marialuigia
authors.initials: M
authors.lastname: Fantacuzzi
authors.forename: Letizia
authors.initials: L
authors.lastname: Giampietro
authors.forename: Pasquale
authors.initials: P
authors.lastname: Linciano
authors.forename: Cristina
authors.initials: C
authors.lastname: Maccallini
authors.forename: Rosa
authors.initials: R
authors.lastname: Amoroso
mesh_terms: D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D047493:PPAR alpha / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047493:PPAR alpha; D013449:Sulfonamides