title: Efficient synthesis and in vitro cytostatic activity of 4-substituted triazolyl-nucleosides.
abstract: We report herein an efficient synthesis of 4-substituted triazolyl-nucleosides and their in vitro cytostatic activity. The synthesis is based on a straightforward 1,3-dipolar cycloaddition between 1-azido-ribose 2 and terminal alkynes under a cooperative effect of microwave activation and copper (I) catalysis. All cycloadducts were obtained in nearly quantitative yield after a short reaction time (1 to 2min). After removal of acetyl protecting groups, the free nucleosides were evaluated against L1210, Molt4/C8, and CEM tumor cell lines. Structure-activity relationship study shows that the substituent on the triazole ring has a major effect since nucleosides 4c and 4g, containing, respectively, a long alkyl chain and an aryl donor group are the most active compounds in this series.
authors.affiliation: Laboratoire de Chimie des Molécules Bioactives et des Arômes, UMR-CNRS 6001, Institut de Chimie de Nice, Université de Nice-Sophia Antipolis, Parc Valrose, F-06108 Nice Cédex 2, France.
authors.forename: Khalid
authors.initials: K
authors.lastname: El Akri
authors.forename: Khalid
authors.initials: K
authors.lastname: Bougrin
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Abdesslem
authors.initials: A
authors.lastname: Faraj
authors.forename: Rachid
authors.initials: R
authors.lastname: Benhida
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007939:Leukemia L1210; D051379:Mice; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D054697:Cytostatic Agents; D009705:Nucleosides; D014230:Triazoles