Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists.
A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.
Giampietro
Letizia
L
Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
Ammazzalorso
Alessandra
A
Giancristofaro
Antonella
A
Lannutti
Fabio
F
Bettoni
Giancarlo
G
De Filippis
Barbara
B
Fantacuzzi
Marialuigia
M
Maccallini
Cristina
C
Petruzzelli
Michele
M
Morgano
Annalisa
A
Moschetta
Antonio
A
Amoroso
Rosa
R
D045744:Cell Line, Tumor; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010100:Oxygen / Q000737:chemistry; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry*; D015533:Transcriptional Activation
D047493:PPAR alpha; D002995:Clofibric Acid; D013455:Sulfur; D010100:Oxygen