2. Academic Validation
  3. Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

  • Eur J Med Chem. 2014 Aug 18:83:498-507. doi: 10.1016/j.ejmech.2014.06.067.
Davide Audisio 1,  Délphine Methy-Gonnot 2,  Christine Radanyi 2,  Jack-Michel Renoir 2,  Stéphanie Denis 2,  Félix Sauvage 2,  Juliette Vergnaud-Gauduchon 2,  Jean-Daniel Brion 1,  Samir Messaoudi 3,  Mouad Alami 4
Affiliations

Affiliations

  • 1 University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
  • 2 Institut Galien-Paris Sud, CNRS, UMR 8612, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France.
  • 3 University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France. Electronic address: samir.messaoudi@u-psud.fr.
  • 4 University Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, LabEx LERMIT, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry F-92296, France. Electronic address: mouad.alami@u-psud.fr.
PMID: 24992077 DOI: 10.1016/j.ejmech.2014.06.067
Abstract

A series of substituted coumarins1-10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human Cancer cells (GI50 = 2-30 μM) and induced a high Apoptosis level in MCF-7 breast Cancer cell line. The molecular signature of HSP90 inhibition was assessed by depletion of the Erα HSP90 client protein.

Keywords

4TCNA; 6BrCaQ; Apoptosis; Cytotoxicity; Hsp90.

Figures