Nucleoside dimers analogs containing floxuridine and thymidine with unnatural linker groups: synthesis and cancer line studies. Part III

Abstract

Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components. Based on analysis of the ³ Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. Google Scholar]J_HH, ³ Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. Google Scholar]J_H1′C2 and ³ Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. Google Scholar]J_H1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).