title: Synthesis, biological evaluation and molecular investigation of fluorinated peroxisome proliferator-activated receptors α/γ dual agonists.
abstract: PPARs are transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new agonists for these receptors. Given that the introduction of fluorine generally has a profound effect on the physical and/or biological properties of the target molecule, we synthesized a series of fluorinated analogs of the previously reported compound 2, some of which turned out to be remarkable PPARα and PPARγ dual agonists. Docking experiments were also carried out to gain insight into the interactions of the most active derivatives with both receptors.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari 'Aldo Moro', Via Orabona 4, 70126 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fracchiolla
authors.forename: Antonio
authors.initials: A
authors.lastname: Laghezza
authors.forename: Luca
authors.initials: L
authors.lastname: Piemontese
authors.forename: Mariagiovanna
authors.initials: M
authors.lastname: Parente
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pochetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Montanari
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Giovanni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carbonara
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
mesh_terms: D001665:Binding Sites; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D054879:Halogenation; D006801:Humans; D008958:Models, Molecular; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D047493:PPAR alpha; D047495:PPAR gamma