title: In vitro toxicity of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of doxifluridine: a bioanalytical investigation.
abstract: The cytotoxicity of N3-methyl-5'-deoxy-5-fluorouridine (N3-Me-5'-dFUR), a novel metabolite of the anticancer pro-drug 5'-deoxy-5-fluorouridine (5'-dFUR), has been evaluated by in vitro experiments with cultures of different cancer cell lines. The new metabolic product was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC-UV) analysis of the incubation mixture. The biomethylation process leading to N3-Me-5'-dFUR could be considered as a possible detoxification pathway, altering the drug bioavailability, in competition with 5'-dFUR cleavage to the active 5-FU.
authors.affiliation: Dipartimento di Chimica, Università degli Studi della Basilicata, Potenza, Italy.
authors.forename: C G
authors.initials: CG
authors.lastname: Zambonin
authors.forename: A
authors.initials: A
authors.lastname: Aresta
authors.forename: M
authors.initials: M
authors.lastname: Grano
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008745:Methylation; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C103213:N(3)-methyl-5'-deoxy-5-fluorouridine; D005467:Floxuridine