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

Delta 2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPAR gamma-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 mu M on various cancer cell lines. Furthermore, five of them showed hepatocyte viability of 80% or more at 200 mu M. In addition, compounds 17 and 18 exhibited promising maximum tolerated doses on a murine model, enabling future investigations. (C) 2014 Elsevier Masson SAS. All rights reserved.