N'est plus au Laboratoire.
GUILLON Remy
Thème de Recherche: temp
remguillon
yahoo.fr
Domaines de Recherche: - Chimie/Chimie analytique
- Chimie/Chimie thérapeutique
- Sciences du Vivant/Biochimie, Biologie Moléculaire/Biochimie
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Productions scientifiques :
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Identification of noncompetitive inhibitors of cytosolic 5′-nucleotidase II using a fragment-based approach
Auteur(s): Marton Zsuzsanna, Guillon R., Krimm Isabelle, Rahimova Rahila, Egron D., Jordheim Lars P., Aghajari Nushin, Dumontet Charles, Perigaud C., Lionne Corinne, Peyrottes S., Chaloin Laurent
(Article) Publié:
European Journal Of Medicinal Chemistry, vol. 58 p.9680-9696 (2015)
Ref HAL: hal-01251800_v1
PMID 26599519
DOI: 10.1021/acs.jmedchem.5b01616
Résumé: We used a combined approach based on fragment-based drug design (FBDD) and in silico methods to design potential inhibitors of the cytosolic 5'-nucleotidase II (cN-II), which has been recognized as an important therapeutic target in hematological cancers. Two subgroups of small compounds (including adenine and biaryl moieties) were identified as cN-II binders and a fragment growing strategy guided by molecular docking was considered. Five compounds induced a strong inhibition of the 5'-nucleotidase activity in vitro, and the most potent ones were characterized as noncompetitive inhibitors. Biological evaluation in cancer cell lines showed synergic effect with selected anticancer drugs. Structural studies using X-ray crystallography lead to the identification of new binding sites for two derivatives and of a new crystal form showing important domain swapping. Altogether, the strategy developed herein allowed identifying new original noncompetitive inhibitors against cN-II that act in a synergistic manner with well-known antitumoral agents.
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