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Electrophilic 5‐Substituted Uracils as Potential Radiosensitizers: A Density Functional Theory Study
Author(s) -
Makurat Samanta,
ChomiczMańka Lidia,
Rak Janusz
Publication year - 2016
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201600240
Subject(s) - chemistry , context (archaeology) , electrophile , density functional theory , combinatorial chemistry , radiosensitizer , computational chemistry , deoxyuridine , dna , radiation therapy , biochemistry , biology , medicine , paleontology , catalysis
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.