title: In Vitro and in Vivo Evaluation of Fully Substituted (5-(3-Ethoxy-3-oxopropynyl)-4-(ethoxycarbonyl)-1,2,3-triazolyl-glycosides as Original Nucleoside Analogues to Circumvent Resistance in Myeloid Malignancies.
abstract: A series of nucleoside analogues bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy. Compound 4a also proved efficient in vivo on mice xenografted with SKM1-R MDS cell line. Additionally, some insights in its mode of action revealed that this compound induced cell death by caspase and autophagy induction.
authors.affiliation: Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.
authors.forename: Hella
authors.initials: H
authors.lastname: Amdouni
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Robert
authors.affiliation: Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.|Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculté des Sciences, Université Mohammed V , B.P. 1014, Rabat, Morocco.
authors.forename: Mohsine
authors.initials: M
authors.lastname: Driowya
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Nathan
authors.initials: N
authors.lastname: Furstoss
authors.affiliation: Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Métier
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Alix
authors.initials: A
authors.lastname: Dubois
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Maeva
authors.initials: M
authors.lastname: Dufies
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Marwa
authors.initials: M
authors.lastname: Zerhouni
authors.affiliation: Centre Commun de Microscopie Appliquée , 06108 Nice, France.
authors.forename: François
authors.initials: F
authors.lastname: Orange
authors.affiliation: Centre Commun de Microscopie Appliquée , 06108 Nice, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lacas-Gervais
authors.affiliation: Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Faculté des Sciences, Université Mohammed V , B.P. 1014, Rabat, Morocco.
authors.forename: Khalid
authors.initials: K
authors.lastname: Bougrin
authors.affiliation: Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.
authors.forename: Anthony R
authors.identifier: 0000-0001-6187-6979
authors.initials: AR
authors.lastname: Martin
authors.affiliation: Centre Méditerranéen de Médecine Moléculaire, Université Côte d'Azur, UMR INSERM U1065 , 06204 Nice, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Auberger
authors.affiliation: Institut de Chimie de Nice UMR7272, Université Côte d'Azur, CNRS , 06108 Nice, France.
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008819:Mice, Nude; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D014230:Triazoles