Why Does the Type of Halogen Atom Matter for the Radiosensitizing Properties of 5-Halogen Substituted 4-Thio-2'-Deoxyuridines?
Cell Line, Tumor
Cell Survival
/ drug effects
Chromatography, High Pressure Liquid
Chromatography, Liquid
Halogens
/ chemistry
Histones
/ metabolism
Humans
Models, Molecular
Molecular Conformation
Molecular Structure
Radiation-Sensitizing Agents
/ chemistry
Tandem Mass Spectrometry
Thiouridine
/ analogs & derivatives
cellular response
modified nucleosides
pulse radiolysis
radiosensitizers
stationary radiolysis
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
02 Aug 2019
02 Aug 2019
Historique:
received:
17
07
2019
revised:
30
07
2019
accepted:
31
07
2019
entrez:
7
8
2019
pubmed:
7
8
2019
medline:
7
1
2020
Statut:
epublish
Résumé
Radiosensitizing properties of substituted uridines are of great importance for radiotherapy. Very recently, we confirmed 5-iodo-4-thio-2'-deoxyuridine (ISdU) as an efficient agent, increasing the extent of tumor cell killing with ionizing radiation. To our surprise, a similar derivative of 4-thio-2'-deoxyuridine, 5-bromo-4-thio-2'-deoxyuridine (BrSdU), does not show radiosensitizing properties at all. In order to explain this remarkable difference, we carried out a radiolytic (stationary and pulse) and quantum chemical studies, which allowed the pathways to all radioproducts to be rationalized. In contrast to ISdU solutions, where radiolysis leads to 4-thio-2'-deoxyuridine and its dimer, no dissociative electron attachment (DEA) products were observed for BrSdU. This observation seems to explain the lack of radiosensitizing properties of BrSdU since the efficient formation of the uridine-5-yl radical, induced by electron attachment to the modified nucleoside, is suggested to be an indispensable attribute of radiosensitizing uridines. A larger activation barrier for DEA in BrSdU, as compared to ISdU, is probably responsible for the closure of DEA channel in the former system. Indeed, besides DEA, the XSdU anions may undergo competitive protonation, which makes the release of X
Identifiants
pubmed: 31382376
pii: molecules24152819
doi: 10.3390/molecules24152819
pmc: PMC6695862
pii:
doi:
Substances chimiques
Halogens
0
Histones
0
Radiation-Sensitizing Agents
0
Thiouridine
13957-31-8
4-thio-2'-deoxyuridine
5580-20-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Narodowe Centrum Nauki
ID : 2014/14/A/ST4/00405
Organisme : Narodowe Centrum Nauki
ID : 2018/28/C/ST4/00479
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