title: Structural development studies of PPARs ligands based on tyrosine scaffold.
abstract: PPARs are nuclear receptors with a critical physiological role in lipid and glucose metabolism. As part of our effort to develop new and selective PPAR agonists containing stilbene and its bioisoster phenyldiazene, novel analogs were synthesized starting from tyrosine and evaluated as PPAR agonists. We tested the effects of phenyloxazole replacement of GW409544, a well-known PPARα/γ dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPARγ agonists. Molecular docking studies performed on these new compounds complemented the experimental results and allowed to gain some insights into the nature of binding of the ligands.
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Linciano
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ammazzalorso
authors.affiliation: Dipartimento di Farmacia, "Drug Discovery" Laboratory, Università degli Studi di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Giovanni
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Marialuigia
authors.initials: M
authors.lastname: Fantacuzzi
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Giampietro
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, 70126 Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Laghezza
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Maccallini
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, 70126 Bari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.affiliation: Dipartimento di Farmacia, "Drug Discovery" Laboratory, Università degli Studi di Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy. Electronic address: antonio.lavecchia@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, 70126 Bari, Italy. Electronic address: fulvio.loiodice@uniba.it.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
authors.affiliation: Dipartimento di Farmacia, Università "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: ramoroso@unich.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Amoroso
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D014443:Tyrosine
keywords: PPARs; PPARγ agonist; Phenyldiazene; Stilbene; Tyrosine