2. Academic Validation
  3. New desulfured troglitazone derivatives: Improved synthesis and biological evaluation

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

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: michel.boisbrun@univ-lorraine.fr.
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.

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