Synthesis and evaluation of new designed multiple ligands directed towards both peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor.
Fiche publication
Date publication
août 2018
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOISBRUN Michel, Pr FLAMENT Stéphane, Dr GRILLIER-VUISSOZ Isabelle
Tous les auteurs :
Meyer M, Foulquier S, Dupuis F, Flament S, Grimaud L, Henrion D, Lartaud I, Monard G, Grillier-Vuissoz I, Boisbrun M
Lien Pubmed
Résumé
Because of the complex biological networks, many pathologic disorders fail to be treated with a molecule directed towards a single target. Thus, combination therapies are often necessary, but they have many drawbacks. An alternative consists in building molecules intended to interact with multiple targets, called designed multiple ligands. We followed such a strategy in order to treat metabolic syndrome, by setting up molecules directed towards both type 1 angiotensin II (AT) receptor and peroxisome proliferator-activated receptor-γ (PPAR-γ). For this purpose, many molecules were prepared by merging both pharmacophores following three different strategies. Their ability to activate PPAR-γ and to block AT receptors were evaluated in vitro. This strategy led to the preparation of many new PPAR-γ activating and AT blocking molecules. Among them, some exhibited both activities, highlighting the convenience of this approach.
Mots clés
AT(1), Chromane, Designed multiple ligands, Imidazole, PPAR-γ, Triazole
Référence
Eur J Med Chem. 2018 Aug 31;158:334-352