Why does the type of halogen atom matter for the radiosensitizing properties of 5-halogen substituted 4-thio-2′-deoxyuridines?
Paulina Spisz , Magdalena Zdrowowicz , Samanta Makurat , Witold Kozak , Konrad Skotnicki , Krzysztof Bobrowski , Janusz Rak
AbstractRadiosensitizing 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− kinetically forbidden.
|Journal series||Molecules, ISSN 1420-3049, (N/A 100 pkt)|
|Publication size in sheets||0.8|
|Keywords in English||radiosensitizers, stationary radiolysis, pulse radiolysis, modified nucleosides, cellular response|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 07-01-2020, ArticleFromJournal|
|Publication indicators||= 0; : 2017 = 1.146; : 2018 = 3.06 (2) - 2018=3.38 (5)|
|Citation count*||1 (2020-01-14)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.