2. Academic Validation
  3. Synthesis of novel 3-halo-3-nitroflavanones and their activities as DNA methyltransferase inhibitors in cancer cells

Synthesis of novel 3-halo-3-nitroflavanones and their activities as DNA methyltransferase inhibitors in cancer cells

  • Eur J Med Chem. 2020 Jan 15;186:111829. doi: 10.1016/j.ejmech.2019.111829.
Dany Pechalrieu 1,  Daniel Dauzonne 2,  Paola B Arimondo 3,  Marie Lopez 4
Affiliations

Affiliations

  • 1 Epigenetic Targeting of Cancer (ETaC), CNRS FRE3600, 118 Route de Narbonne, 31062, Toulouse Cedex 9, France.
  • 2 CNRS, UMR3666, INSERM, U1143, Institut Curie, Centre de Recherche, 26 Rue D'Ulm, 75248, Paris Cedex 05, France.
  • 3 Epigenetic Targeting of Cancer (ETaC), CNRS FRE3600, 118 Route de Narbonne, 31062, Toulouse Cedex 9, France; Epigenetic Chemical Biology, Institut Pasteur, CNRS UMR3523, 28 Rue Du Dr Roux, 75015, Paris, France.
  • 4 Epigenetic Targeting of Cancer (ETaC), CNRS FRE3600, 118 Route de Narbonne, 31062, Toulouse Cedex 9, France; Institut des Biomolécules Max Mousseron (IBMM), CNRS, Univ Montpellier, ENSCM UMR 5247, 240 Avenue Du Prof. E. Jeanbrau, 34296, Montpellier Cedex 5, France. Electronic address: [email protected].
PMID: 31757526 DOI: 10.1016/j.ejmech.2019.111829
Abstract

The implication of DNA methylation in Cancer is today clearly established. Despite that nucleoside analogues are currently used for leukaemia treatment, their low stability in physiological conditions and their lack of selectivity arise the need for the identification of non-nucleoside DNA Methyltransferase inhibitors. Here, we describe the synthesis and pharmacological characterisation of a novel class of DNA Methyltransferase inhibitors: the 3-halo-3-nitroflavanones. We showed that 3-bromo-3-nitroflavanones 3b and 4a have a micromolar DNMT inhibition and an increased potency in a cell reporter model. Interestingly they are significantly more stable than the reference compounds and induce a low cytotoxicity, supporting them as new candidates for the development of non-cytotoxic cell-reprogramming epi-drugs for Anticancer treatment.

Keywords

Anticancer therapy; DNA methylation; DNMT inhibitor; Epigenetics; Flavanone.

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