Synthesis of Naphthyl-, Quinolin- and Anthracenyl Analogues of Clofibric Acid as PPARα Agonists.
PPARα is a ligand activated transcription factor belonging to the nuclear receptor subfamily, involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPARα activation is important in steatosis, inflammation and fibrosis in preclinical models of non-alcoholic fatty liver disease identifying a new potential therapeutic area. In this work, three series of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized. In an effort to obtain new compounds active as PPARα agonists, these molecules were evaluated for PPARα transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPARα; noteworthy, optically active naphthyl derivatives activated PPARα better than corresponding parent compound.
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Letizia
L
Giampietro
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Alessandra
A
Ammazzalorso
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Isabella
I
Bruno
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Simone
S
Carradori
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Barbara
B
De Filippis
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Marialuigia
M
Fantacuzzi
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Antonella
A
Giancristofaro
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Cristina
C
Maccallini
Dipartimento di Farmacia, Università "G. d'Annunzio" di Chieti, via dei Vestini, 66100, Chieti, Italy.
Rosa
R
Amoroso
D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D047493:PPAR alpha / Q000819:agonists*
D047493:PPAR alpha; D002995:Clofibric Acid
anthracenyl; clofibric acid; naphthyl; peroxisome proliferator-activated receptor agonist; quinolin; transactivation assay