TY - JOUR
T1 - Screening of X-ray responsive substances for the next generation of radiosensitizers
AU - Moriyama, Akihiro
AU - Hasegawa, Takema
AU - Jiang, Lei
AU - Iwahashi, Hitoshi
AU - Mori, Takashi
AU - Takahashi, Junko
N1 - Funding Information:
This research was partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research from AMED under Grant Number JP17am0101086. This work was supported by JSPS KAKENHI Grant Number JP18H02705 and 19K22609. This work was also supported by the Canon Foundation Number K16-0073. We would like to thank Editage for English language editing.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - X-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3’-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.
AB - X-ray responsivity resulting in the generation of reactive oxygen species (ROS) was investigated in 9600 organic compounds that were selected by considering their structural diversity. We focused on superoxides that were primarily detected using dihydroethidium (DHE) and hydroxyl radicals, that were identified fluorometrically using 3’-(p-aminophenyl) Fluorescein (APF). Many organic compounds were discovered that responded to the DHE and/or APF assay using X-ray irradiation. These results suggest that some of these organic compounds emit either superoxides or hydroxyl radicals whereas others emit both under the influence of X-ray irradiation. The response of the derivatives of a hit compound with a partial change in the structure was also investigated. The products produced from DHE by X-ray irradiation were identified by HPLC to confirm the integrity of the process. Although, the reactions were suppressed by the superoxide dismutase (SOD), not only 2-hydroxyethidium (2-OH-E+), but also ethidium (E+) were detected. The results suggest that apart from a direct reaction, an indirect reaction may occur between DHE and the superoxides. Although X-ray responsiveness could not be inferred due to the molecular complexity of the investigated compounds, delineation of these reactions will facilitate the development of the next generation of radiosensitizers.
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U2 - 10.1038/s41598-019-54649-2
DO - 10.1038/s41598-019-54649-2
M3 - Article
C2 - 31796788
AN - SCOPUS:85075944898
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 18163
ER -