Title :

Anti-diabetic activity of fused PPAR gamma-SIRT1 ligands with limited body-weight gain by mimicking calorie restriction and decreasing SGK1 expression

Author(s) :

Pirat, Celine [Auteur]
Dacquet, Catherine [Auteur]
Leclerc, Veronique [Auteur]
Hennuyer, Nathalie [Auteur]
Beucher-Gaudin, Monique [Auteur]
Zanirato, Ghislaine [Auteur]
Geant, Anne [Auteur]
Staels, Bart [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011
Récepteurs nucléaires, maladies cardiovasculaires et diabète [EGID]
Ktorza, Alain [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Lille Inflammation Research International Center [LIRIC]
Caignard, Daniel-Henri [Auteur]
Berthelot, Pascal [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer [JPArc - U837 Inserm]
Lebegue, Nicolas [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer [JPArc - U837 Inserm]

Journal title :

European journal of medicinal chemistry

Abbreviated title :

Eur. J. Med. Chem.

Volume number :

137

Pages :

310-326

Publication date :

2017-09-08

ISSN :

0223-5234

English keyword(s) :

SGK1
SIRT1
PPAR
Diabetes
Resveratrol
Calorie restriction
Body-weight gain

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the ...
Show more >A series of benzothiazol-2-one containing α-ethoxyphenylpropionic acid derivatives incorporating resveratrol or butein scaffolds were designed as fused full PPARγ agonist ligands and SIRT1-activating compounds for the treatment of type 2 diabetes (T2D) and its complications. Compound 14d displayed the best in vitro pharmacological profile with full PPARγ agonist activity (Emax = 98%, EC = 200 nM), SIRT1 enzymatic activation (+128%) and SGK1 expression inhibition (- 57%) which is known to limit side effects as fluid retention and body-weight gain. Compound 14d showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain by mimicking calorie restriction (CR) and inhibiting SGK1 expression.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille
Institut Pasteur de Lille

Collections :

• Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
• Lille Inflammation Research International Center (LIRIC) - U995
• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:42Z