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 PPAR alpha/gamma dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPAR gamma 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

DE FILIPPIS, Barbara;LINCIANO, PASQUALE;AMMAZZALORSO, Alessandra;FANTACUZZI, MARIALUIGIA;GIAMPIETRO, Letizia;MACCALLINI, Cristina;AMOROSO, Rosa
2015-01-01

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 PPAR alpha/gamma dual agonist, with stilbene or phenyldiazene moiety, spaced by an ether bridge to tyrosine portion. These structural modifications provided potent and selective PPAR gamma 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/586310
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