title: From 5-fluorouracil acyclonucleosides to benzo-fused six- and seven-membered rings linked to pyrimidine and purine bases: the shift from differentiating anticancer agents to apoptotic inducers.
abstract: BACKGROUND
  (RS)-1-{[3-(2-Hydroxyethoxy)-1-isopropoxy]propyl}-5-fluorouracil proved to be a good differentiating agent against rhabdomyosarcoma cells.
  
  
  OBJECTIVE
  As lipophilicity is known to affect the anticancer activity, the synthesis of a wide range of 5-fluorouracil derivatives linked to benzo-fused seven-membered rings was undertaken.
  
  
  METHODS
  The decision was then made to change 5-fluorouracil for uracil, with the prospect of finding an antiproliferative agent endowed with a new mechanism of action. Later on, pyrimidines were substituted for purines. Completing a structure-activity relationship study, a series of isosteric seven-membered derivatives were prepared.
  
  
  CONCLUSIONS
  Finally, molecules were designed in which both structural entities (such as the benzoheterocycle and the purine) were linked through a strong C-C bond. The anticancer activity for the most active compounds was correlated with their capability to induce apoptosis.
authors.affiliation: Universidad de Granada, Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, c/Campus de Cartuja s/n, 18071 Granada, Spain ++34 958 243848 ; ++34 958 243845 ; jmcampos@ugr.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Conejo-García
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Núñez
authors.forename: Mónica
authors.initials: M
authors.lastname: Díaz-Gavilán
authors.forename: Olga
authors.initials: O
authors.lastname: Cruz-López
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Gallo
authors.forename: Antonio
authors.initials: A
authors.lastname: Espinosa
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos