title: Electrophilic 5-Substituted Uracils as Potential Radiosensitizers: A Density Functional Theory Study.
abstract: Although 5-bromo-2'-deoxyuridine (5BrdU) possesses significant radiosensitizing power in vitro, clinical studies do not confirm any advantages of radiotherapy employing 5BrdU. This situation calls for a continuous search for efficient radiosensitizers. Using the proposed mechanism of radiosensitization by 5BrdU, we propose a series of 5-substituted uracils, XYU, that should undergo efficient dissociative electron attachment. The DFT-calculated thermodynamic and kinetic data concerning the XYU degradations induced by electron addition suggests that some of the scrutinized derivatives have much better characteristics than 5BrdU itself. Synthesis of these promising candidates for radiosensitizers, followed by studies of their radiosensitizing properties in DNA context, and ultimately in cancer cells, are further steps to confirm their potential applicability in anticancer treatment.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland.
authors.forename: Samanta
authors.initials: S
authors.lastname: Makurat
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland. lidia.chomicz@ug.edu.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Chomicz-Mańka
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308, Gdańsk, Poland. janusz.rak@ug.edu.pl.
authors.forename: Janusz
authors.initials: J
authors.lastname: Rak
mesh_terms: D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D011838:Radiation-Sensitizing Agents / Q000737:chemistry*; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D011838:Radiation-Sensitizing Agents; D014498:Uracil
keywords: DNA; density functional calculations; dissociative electron attachment; nucleobases; radiopharmaceuticals