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Synthesis of triazolylmethyl-linked nucleoside analogs via combination of azidofuranoses with propargylated nucleobases and study on their cytotoxicity

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Chemistry of Heterocyclic Compounds Aims and scope

Copper(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition reactions (CuAAC) between azidofuranoses and propargyl-nucleobases were carried out in the presence of CuSO4·5H2O and sodium ascorbate as catalytic system to provide the corresponding 1,4-disubstituted-1,2,3-triazole-bridged nucleoside analogs in good yields. Twelve new sugar-based triazolylmethyl-linked nucleoside analogs were synthesized and screened for their cytotoxic activity against MDA-MB-231, Hep3B, PC-3, SH-SY5Y, and HCT-116 cancer cell lines and control cell line (L929). Most of the compounds were moderately effective against all the cancer cell lines assayed. Particularly, among the tested compounds, 1,2,3-triazole-linked 5-fluorouracil–mannofuranose hybrid was found to be the most potent cytotoxic agent against HCT-116, Hep3B, SH-SY5Y cells with IC50 values of 35.6, 71.1, and 75.6 μM, respectively. None of the triazolylmethyl-linked nucleoside analogs exhibited cytotoxic effect against the control cells L929.

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This work was supported by TUBITAK-Research Council of Turkey with the project number 114Z757. Author E. Halay also offers his profound thanks to TUBITAK-BIDEB 2211A for their bursary support.

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Authors and Affiliations

  1. Scientific Analysis Technological Application and Research Center, Uşak University, 1 Eylul Campus, 64500, Uşak, Turkey

    Erkan Halay

  2. Department of Food Technology, Şebinkarahisar School of Applied Sciences, Giresun University, Yayci Village, 28800, Giresun, Turkey

    Emriye Ay

  3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, İnönü University, Elazığ Highway, 44280, Malatya, Turkey

    Emine Şalva

  4. Department of Chemistry, Faculty of Arts and Sciences, Manisa Celal Bayar University, Şehit Prof. Dr. İlhan Varank Campus, 45030, Manisa, Turkey

    Kadir Ay

  5. Department of Chemistry, Faculty of Science, Ege University, Erzene St, 35100, İzmir, Turkey

    Tamer Karayıldırım

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  1. Erkan Halay
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  2. Emriye Ay
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Correspondence to Kadir Ay.

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We dedicated this article to Prof. Dr. Hüseyin Anıl for his 70th birthday.

He influenced our lives and our thinking in a very positive way.

Supplementary information file containing spectral data of the synthesized compounds is available at the journal website at http://link.springer.com/journal/10593.

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2018, 54(2), 158–166

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Halay, E., Ay, E., Şalva, E. et al. Synthesis of triazolylmethyl-linked nucleoside analogs via combination of azidofuranoses with propargylated nucleobases and study on their cytotoxicity. Chem Heterocycl Comp 54, 158–166 (2018). https://doi.org/10.1007/s10593-018-2248-4

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