Abstract

The effects resulting from the introduction of an oxime group in place of the distal aromatic ring of the diphenyl moiety of LT175, previously reported as a PPARalpha/gamma dual agonist, have been investigated. This modification allowed the identification of new bioisosteric ligands with fairly good activity on PPARalpha and fine-tuned moderate activity on PPARgamma. For the most interesting compound (S)-3, docking studies in PPARalpha and PPARgamma provided a molecular explanation for its different behavior as full and partial agonist of the two receptor isotypes, respectively. A further investigation of this compound was carried out performing gene expression studies on HepaRG cells. The results obtained allowed to hypothesize a possible mechanism through which this ligand could be useful in the treatment of metabolic disorders. The higher induction of the expression of some genes, compared to selective agonists, seems to confirm the importance of a dual PPARalpha/gamma activity which probably involves a synergistic effect on both receptor subtypes.

Autore Pugliese

• Laghezza Antonio , Carrieri Antonio , Loiodice Fulvio , Fracchiolla Giuseppe , Piemontese Luca , Tortorella Paolo

Tutti gli autori

• LAGHEZZA A.;CARRIERI A.;LOIODICE F.;FRACCHIOLLA G.;CARBONARA G.G.;PIEMONTESE L.;TORTORELLA P.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2015

ISSN

0223-5234

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

13

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile