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.
Dipartimento di Scienze del Farmaco, Università degli Studi G. d'Annunzio, Chieti, Italy.
Letizia
L
Giampietro
Alessandra
A
Ammazzalorso
Antonella
A
Giancristofaro
Fabio
F
Lannutti
Giancarlo
G
Bettoni
Barbara
B
De Filippis
Marialuigia
M
Fantacuzzi
Cristina
C
Maccallini
Michele
M
Petruzzelli
Annalisa
A
Morgano
Antonio
A
Moschetta
Rosa
R
Amoroso
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