2. Academic Validation
  3. Aurones as histone deacetylase inhibitors: identification of key features

Aurones as histone deacetylase inhibitors: identification of key features

  • Bioorg Med Chem Lett. 2014 Dec 1;24(23):5497-501. doi: 10.1016/j.bmcl.2014.10.019.
Vincent Zwick 1,  Alkiviadis-Orfefs Chatzivasileiou 2,  Nathalie Deschamps 1,  Marina Roussaki 2,  Claudia A Simões-Pires 1,  Alessandra Nurisso 1,  Iza Denis 3,  Christophe Blanquart 4,  Nadine Martinet 5,  Pierre-Alain Carrupt 1,  Anastasia Detsi 6,  Muriel Cuendet 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
  • 2 Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece.
  • 3 INSERM, UMR892, F-44000 Nantes, France; CNRS, UMR6299, F-44000 Nantes, France; Université Nantes, F-44000 Nantes, France.
  • 4 INSERM, UMR892, F-44000 Nantes, France; CNRS, UMR6299, F-44000 Nantes, France; Université Nantes, F-44000 Nantes, France; Réseau Epigénétique du Canceropôle Grand Ouest, France.
  • 5 Institut de chimie, UMR CNRS 7272, UNSA, F-06108 Nice, France.
  • 6 Laboratory of Organic Chemistry, School of Chemical Engineering, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece. Electronic address: adetsi@chemeng.ntua.gr.
  • 7 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Electronic address: muriel.cuendet@unige.ch.
PMID: 25455492 DOI: 10.1016/j.bmcl.2014.10.019
Abstract

In this study, a total of 22 Flavonoids were tested for their HDAC inhibitory activity using fluorimetric and BRET-based assays. Four aurones were found to be active in both assays and showed IC50 values below 20 μM in the enzymatic assay. Molecular modelling revealed that the presence of hydroxyl groups was responsible for good compound orientation within the isoenzyme catalytic site and zinc chelation.

Keywords

Aurone; Docking; Histone deacetylase; Structure activity relationship.

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