2. Academic Validation
  3. Modular synthesis of new C-aryl-nucleosides and their anti-CML activity

Modular synthesis of new C-aryl-nucleosides and their anti-CML activity

  • Bioorg Med Chem Lett. 2018 Jun 1;28(10):1931-1936. doi: 10.1016/j.bmcl.2018.03.063.
Hamid Marzag 1,  Marwa Zerhouni 2,  Hamza Tachallait 1,  Luc Demange 3,  Guillaume Robert 2,  Khalid Bougrin 4,  Patrick Auberger 2,  Rachid Benhida 5
Affiliations

Affiliations

  • 1 Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France; Plant Chemistry, Organic and Bioorganic Synthesis Team, URAC23, Faculty of Sciences, B.P. 1014, GEOPAC Research Center, Mohammed V University, Rabat, Morocco.
  • 2 Université Côte d'Azur, INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Bâtiment ARCHIMED, 151 Route de Saint-Antoine de Ginestière, BP 2 3194, 06204 Nice Cedex 3, France.
  • 3 Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France; Département de Chimie, Université Paris Descartes, Sorbonne Paris Cité, UFR des Sciences Pharmaceutiques, 4 avenue de l'Observatoire & UFR Biomédicale des Saints Pères, 45 rue des Saints Pères, Paris Fr-75006, France.
  • 4 Plant Chemistry, Organic and Bioorganic Synthesis Team, URAC23, Faculty of Sciences, B.P. 1014, GEOPAC Research Center, Mohammed V University, Rabat, Morocco.
  • 5 Université Côte d'Azur, CNRS, Institut de Chimie de Nice UMR 7272, 06108 Nice, France; Mohamed VI Polytechnic University, UM6P, 43150 Ben Guerir, Morocco. Electronic address: benhida@unice.fr.
PMID: 29655981 DOI: 10.1016/j.bmcl.2018.03.063
Abstract

The C-aryl-ribosyles are of utmost interest for the development of Antiviral and Anticancer agents. Even if several synthetic pathways have been disclosed for the preparation of these nucleosides, a direct, few steps and modular approaches are still lacking. In line with our previous efforts, we report herein a one step - eco-friendly β-ribosylation of aryles and heteroaryles through a direct Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf)3. The resulting carbohydrates have been functionalized by cross-coupling reactions, leading to a series of new C-aryl-nucleosides (32 compounds). Among them, we observed that 5d exerts promising anti-proliferative effects against two human Chronic Myeloid Leukemia (CML) cell lines, both sensitive (K562-S) or resistant (K562-R) to imatinib, the "gold standard of care" used in this pathology. Moreover, we demonstrated that 5d kills CML cells by a non-conventional mechanism of cell death.

Keywords

Anti-CML agents; Green chemistry; Modular syntheses; Nucleoside analogues.

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