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

HALAY E., Ay E., ŞALVA E., Ay K., KARAYILDIRIM T.

Chemistry of Heterocyclic Compounds, cilt.54, sa.2, ss.158-166, 2018 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 54 Sayı: 2
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1007/s10593-018-2248-4
  • Dergi Adı: Chemistry of Heterocyclic Compounds
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.158-166
  • Anahtar Kelimeler: anticancer activity, azido sugars, click chemistry, nucleobases, nucleosides, triazoles
  • Uşak Üniversitesi Adresli: Evet

Özet

[Figure not available: see fulltext.] 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.