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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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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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