3-Halo-3-nitro-aza/thioflavanones: DNMT inhibitors with a two-site binding mode in the hDNMT3A catalytic pocket
Flavonoid derivatives are natural product analogues that have shown great interest for therapeutic applications as modulators of DNA methylation. In this article we report new synthesis pathways to access ten novel flavonoid derivatives (i.e. 3-halo-3-nitro-aza/thioflavanones) to be used as potential DNA methyltransferase inhibitors. These compounds have a micromolar inhibition against human DNA methyltransferase 3A in our in vitro fluorescence-based assay. Importantly, a docking study of representative compounds of this series in the enzyme pocket highlights a mode of interaction in the catalytic pocket of hDNMT3A that has never been described.
Authors
- Marie Lopez (ORCID: https://orcid.org/0000-0001-7479-4657)
- Francesco Calzaferri (ORCID: https://orcid.org/0000-0002-4781-2925)
- Maxime Louet (ORCID: https://orcid.org/0000-0002-5840-2147)
- Paola B. Arimondo
- Jean‐Yves Winum (ORCID: https://orcid.org/0000-0003-3197-3414)
- Arie Van-Der-Lee
- Alexandra Serhouni
- Yannick Bessina
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Epigénétique et Destin Cellulaire (FR)
- Institut des Biomolécules Max Mousseron (FR)
- Institut Européen des Membranes (FR)
Publication Details
- Journal
- Bioorganic & Medicinal Chemistry
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1016/j.bmc.2024.117988
- Citations
- 2
- Primary Topic
- Nuclear Receptors and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.54
Funders
- Fondation ARC pour la Recherche sur le Cancer
- Ministère de l'Enseignement Supérieur et de la Recherche
- Centre National de la Recherche Scientifique
- Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
- Australian Research Council