New desulfured troglitazone derivatives: Improved synthesis and biological evaluation

  • Eur J Med Chem. 2020 Feb 1:187:111939. doi: 10.1016/j.ejmech.2019.111939.
Dorian Dupommier  1 ,  Claire Muller  2 ,  Corinne Comoy  1 ,  Sabine Mazerbourg  2 ,  Andrea Bordessa  1 ,  Eline Piquard  1 ,  Manon Pawlak  1 ,  Flavian Piquard  1 ,  Hélène Martin  3 ,  Elia De Fays  2 ,  Stéphanie Grandemange  2 ,  Stéphane Flament  2 ,  Michel Boisbrun  4
Affiliations
  • 1. Université de Lorraine, CNRS, L2CM, F-54000, Nancy, France.
  • 2. Université de Lorraine, CNRS, CRAN, F-54000, Nancy, France.
  • 3. PEPITE EA4267, Univ. Bourgogne Franche-Comté, F-25000, Besançon, France.
  • 4. Université de Lorraine, CNRS, L2CM, F-54000, Nancy, France. Electronic address: [email protected].
PMID: 31838327 DOI: 10.1016/j.ejmech.2019.111939
Abstract

Breast Cancer is a major medical threat which cannot be sufficiently addressed by current therapies because of spontaneous or acquired treatment resistance. Besides, triple-negative breast Cancer (TNBC) tumors do not respond to targeted therapies, thus new therapeutic strategies are needed. In this context, we designed and prepared new desulfured troglitazone (TGZ)-derived molecules and evaluated them in vitro for their anti-proliferative activity, with a special focus on triple-negative breast Cancer cell lines. Optimization of the synthetic strategies and deracemization of the lead compound were performed to give highly active compound 10 with low-micromolar potency. Further studies revealed that this compound triggers Apoptosis rather than cell cycle arrest as observed with TGZ.

Keywords
Apoptosis; Breast cancer; Chromane; Deracemization; Lipase; Troglitazone.