Optimization of troglitazone derivatives as potent anti-proliferative agents: towards more active and less toxic compounds.

Date publication

août 2014

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOISBRUN Michel , Pr FLAMENT Stéphane , Dr GRILLIER-VUISSOZ Isabelle , Dr KUNTZ Sandra , Dr MAZERBOURG Sabine

Tous les auteurs :
Bordessa A, Colin-Cassin C, Grillier-Vuissoz I, Kuntz S, Mazerbourg S, Husson G, Vo M, Flament S, Martin H, Chapleur Y, Boisbrun M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/24953030

Résumé

Delta2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPARgamma-independent manner. We prepared various compounds in order to increase their potency and decrease their toxicity towards non-malignant primary cultured hepatocytes. Many compounds induced viabilities less than 20% at 10 muM on various cancer cell lines. Furthermore, five of them showed hepatocyte viability of 80% or more at 200 muM. In addition, compounds 17 and 18 exhibited promising maximum tolerated doses on a murine model, enabling future investigations.

Référence

Eur J Med Chem. 2014 Aug 18;83:129-40