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, ss.158-166, 2018 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 54 Konu: 2
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1007/s10593-018-2248-4
  • Dergi Adı: CHEMISTRY OF HETEROCYCLIC COMPOUNDS
  • Sayfa Sayıları: ss.158-166

Özet

Copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reactions (CuAAC) between azidofuranoses and propargyl-nucleobases were carried out in the presence of CuSO4 center dot 5H(2)O 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 mu M, respectively. None of the triazolylmethyl-linked nucleoside analogs exhibited cytotoxic effect against the control cells L929.