Recent evidences suggest a moderate activation of Peroxisome Proliferator-Activated Receptors (PPARs) could be favorable in metabolic diseases, reducing side effects given from full agonists. PPAR partial agonists and antagonists represent, to date, interesting tools to better elucidate biological processes modulated by these receptors. In this work are reported new benzenesulfonimide compounds able to block PPARα, synthesized and tested by transactivation assays and gene expression analysis. Some of these compounds showed a dose-dependent antagonistic behavior on PPARα, submicromolar potency, different profiles of selectivity versus PPARγ, and a repressive effect on CPT1A expression. Dockings and molecular dynamics on properly selected benzenesulfonimide derivatives furnished fresh insights into the molecular determinant most likely responsible for PPARα antagonism.

Synthesis, in vitro evaluation, and molecular modelling investigation of benzenesulfonimide Peroxisome Proliferator-Activated Receptors α antagonists

AMMAZZALORSO, Alessandra;VERGINELLI, Fabio;BRUNO, ISABELLA;D'ANGELO, ALESSANDRA;DE FILIPPIS, Barbara;FANTACUZZI, MARIALUIGIA;FLORIO, ROSALBA;GIAMPIETRO, Letizia;GIANCRISTOFARO, ANTONELLA;MACCALLINI, Cristina;CAMA, Alessandro;AMOROSO, Rosa
2016-01-01

Abstract

Recent evidences suggest a moderate activation of Peroxisome Proliferator-Activated Receptors (PPARs) could be favorable in metabolic diseases, reducing side effects given from full agonists. PPAR partial agonists and antagonists represent, to date, interesting tools to better elucidate biological processes modulated by these receptors. In this work are reported new benzenesulfonimide compounds able to block PPARα, synthesized and tested by transactivation assays and gene expression analysis. Some of these compounds showed a dose-dependent antagonistic behavior on PPARα, submicromolar potency, different profiles of selectivity versus PPARγ, and a repressive effect on CPT1A expression. Dockings and molecular dynamics on properly selected benzenesulfonimide derivatives furnished fresh insights into the molecular determinant most likely responsible for PPARα antagonism.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/650004
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact