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ID: ALA4118130

Journal: Bioorg Med Chem Lett

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

Authors: Marzag H, Zerhouni M, Tachallait H, Demange L, Robert G, Bougrin K, Auberger P, Benhida R.

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.

CiteXplore: 29655981

DOI: 10.1016/j.bmcl.2018.03.063