title: 3'-O- and 5'-O-Propargyl Derivatives of 5-Fluoro-2'-Deoxyuridine: Synthesis, Cytotoxic Evaluation and Conformational Analysis.
abstract: A series of new 3'-O- and 5'-O-propargyl derivatives of 5-fluoro-2'-deoxyuridine (1-4) was synthesized by means of propargyl reaction of properly blocked nucleosides (2,4), followed by the deprotection reaction with ammonium fluoride. The synthesized propargylated 5-fluoro-2'-deoxyuridine analogues (1-4) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7), using the sulforhodamine B (SRB) assay. The highest activity and the best SI coefficient in all of the investigated cancer cells were displayed by 3'-O-propargyl-5-fluoro-2'-deoxyuridine (1), and its activity was higher than that of the parent nucleoside. The other new compounds exhibited moderate activity in all of the used cell lines.
authors.affiliation: a Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego St 12/14, 61-704 Poznań , Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Baraniak
authors.affiliation: a Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego St 12/14, 61-704 Poznań , Poland.|b Department of Pharmacology , Faculty of Pharmacy, Poznań University of Medical Sciences , Rokietnicka St 5a, 60-806 Poznań , Poland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baranowski
authors.affiliation: b Department of Pharmacology , Faculty of Pharmacy, Poznań University of Medical Sciences , Rokietnicka St 5a, 60-806 Poznań , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruszkowski
authors.affiliation: a Institute of Bioorganic Chemistry, Polish Academy of Sciences , Noskowskiego St 12/14, 61-704 Poznań , Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Boryski
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: C000614655:3'-O-propargyl-5-fluoro-2'-deoxyuridine; D000970:Antineoplastic Agents; D005467:Floxuridine
keywords: KB and MCF-7; Propargylated 5-fluoro-2′-deoxyuridine derivatives; click chemistry reagents; cytotoxic activity; human cancer cell lines: HeLa; propargyl moiety