PPARs are nuclear receptors with a critical physiological role in lipid and glucose metabolism. As part of our effort to develop new and selective PPAR agonists containing stilbene and its bioisoster phenyldiazene, novel analogs were synthesized starting from tyrosine and evaluated as PPAR agonists. We tested the effects of phenyloxazole replacement of GW409544, a well-known PPARalpha/gamma dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPARgamma agonists. Molecular docking studies performed on these new compounds complemented the experimental results and allowed to gain some insights into the nature of binding of the ligands.
Structural development studies of PPARs ligands based on tyrosine scaffold / Barbara De, Filippis; Pasquale, Linciano; Alessandra, Ammazzalorso; DI GIOVANNI, Carmen; Marialuigia, Fantacuzzi; Letizia, Giampietro; Antonio, Laghezza; Cristina, Maccallini; Paolo, Tortorella; Lavecchia, Antonio; Fulvio, Loiodice; Rosa, Amoroso. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 89:(2015), pp. 817-825. [10.1016/j.ejmech.2014.10.083]
Structural development studies of PPARs ligands based on tyrosine scaffold
DI GIOVANNI, CARMEN;LAVECCHIA, ANTONIO;
2015
Abstract
PPARs are nuclear receptors with a critical physiological role in lipid and glucose metabolism. As part of our effort to develop new and selective PPAR agonists containing stilbene and its bioisoster phenyldiazene, novel analogs were synthesized starting from tyrosine and evaluated as PPAR agonists. We tested the effects of phenyloxazole replacement of GW409544, a well-known PPARalpha/gamma dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPARgamma agonists. Molecular docking studies performed on these new compounds complemented the experimental results and allowed to gain some insights into the nature of binding of the ligands.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
