Abstract

A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARgamma-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARgamma target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARalpha target genes indicating that their in vivo effects stemmed from an activation of both PPARalpha and gamma. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.

Autore Pugliese

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

Tutti gli autori

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

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2012

ISSN

0022-2623

ISBN

Non Disponibile

Numero di citazioni Wos

27

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

27

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile