title: Synthesis of 3'-azido-2',3'-dideoxy-5-fluorouridine phosphoramidates and evaluation of their anticancer activity.
abstract: A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3'-azido-2',3'-dideoxy-5-fluorouridine (12-21) were synthesized by means of phosphorylation of 3'-azido-2',3'-dideoxy-5-fluorouridine (4) with 4-chlorophenyl phosphoroditriazolide (10) followed by a reaction with the appropriate amine. The synthesized phosphoramidates (12-21) 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 in all the investigated cancer cells was displayed by phosphoramidate 13 with the N-ethyl substituent and its activity was much higher than that of the parent nucleoside. Also phosphoramidate 17 with the N-propargyl substituent exhibited good activity in all the used cell lines.
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka St 6, 60-780 Poznań, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Lewandowska
authors.forename: Piotr
authors.initials: P
authors.lastname: Ruszkowski
authors.forename: Dagmara
authors.initials: D
authors.lastname: Baraniak
authors.forename: Anna
authors.initials: A
authors.lastname: Czarnecka
authors.forename: Natalia
authors.initials: N
authors.lastname: Kleczewska
authors.forename: Lech
authors.initials: L
authors.lastname: Celewicz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C587478:3'-azido-2',3'-dideoxy-5-fluorouridine phosphoramidate; D000970:Antineoplastic Agents; D005467:Floxuridine
keywords: 3’-Azido-2′,3′-dideoxy-5-fluorouridine phosphoramidates; Cytotoxic activity; Human cancer cell lines: HeLa, KB and MCF-7; Phosphorylation