Synthesis of new troglitazone derivatives: Anti-proliferative activity in breast cancer cell lines and preliminary toxicological study

Breast cancer is the most prevalent cancer in women. The development of resistances to therapeutic agents and the absence of targeted therapy for triple negative breast cancer motivate the search for alternative treatments. With this aim in mind, we synthesised new derivatives of troglitazone, a compound which was formerly used as an anti-diabetic agent and which exhibits anti-proliferative activity on various cancer cell lines. Among the compounds prepared, some displayed micromolar activity against hormone-dependent and hormone-independent breast cancer cells. Furthermore, the influence of the compounds on the viability of primary cultures of human hepatocytes was evaluated. This enabled us to obtain for the first time interesting structure–toxicity relationships in this family of compounds, resulting in 6b and 8b, which show good anti-proliferative activities and poor toxicity towards hepatocytes, compared to troglitazone.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Synthesis of new troglitazone derivatives is reported.
► Anti-proliferative activity against breast cancer cell lines showed micromolar potency.
► Clear structure–toxicity relationships were assessed in this series of compounds.