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DOI: 10.4121/6244da9d-d869-4596-b922-a35ce39ff123

Liu, Juncheng; Xu, Bing; Denkova, Antonia; Eelkema, Rienk (2024): Data underlying the publication: Organochloride mediated prodrug activation induced by ionizing radiation. Version 1. 4TU.ResearchData. dataset. https://doi.org/10.4121/6244da9d-d869-4596-b922-a35ce39ff123.v1

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Categories

• Organic Chemistry
• Chemical Sciences

Keywords

chemotherapy prodrug radiation chemistry radiotherapy self-immolative linker

Time coverage

2021-2024

Licence

CC0

Interoperability

• RO-Crate Metadata

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by Juncheng Liu , Bing Xu, Antonia Denkova , Rienk Eelkema

Boronic acid and ester-caged prodrugs have been widely investigated in cellular-generated hydrogen peroxide triggered release. Although it is well-known that ionizing radiation generates hydrogen peroxide in aqueous solution, using this approach to activate boronic acid or ester-based prodrugs suffers from low H₂O₂ yields and thus low uncaging efficiency. However, the peroxyl radical formed from irradiating aqueous solution of organochloride may increase the uncaging efficiency. In this study, we used a boronic acid-caged coumarin derivative to quantify the yield of oxidation induced by clinical doses of radiation, and boronic acid-caged gemcitabine to assess the activation of a prodrug upon irradiation. Irradiation of the coumarin derivative in phosphate buffered saline shows a low yield of 0.048 µM/Gy, and the prodrug after irradiation has only limited toxicity to U87 cell line, indicating limited uncaging. The oxidation of boronic acid can be greatly enhanced by the peroxyl radical generated from irradiation of dilute PBS-organochloride solutions, with the yield increasing to 0.13 µM/Gy. Moreover, the oxidation by peroxyl radical can be catalyzed by N,N-dimethylaniline derivatives, increasing the yield to 0.19 µM/Gy. Clinical dose irradiation of the caged gemcitabine derivative in a solution of PBS with trichloroethanol and 2-(dimethylamino)benzoic acid shows efficient tumor cell killing and a comparable toxicity with that of the parent drug, indicating efficient uncaging.

History

• 2024-10-18 first online, published, posted

Publisher

4TU.ResearchData

Format

fluorescence spectrum raw data.jws & .txt; plotted spectrum.opju; cell experiment data.pzfx; exported graph.tif; NMR data.mnova

Funding

• China Scholarship Council (CSC)

Organizations

TU Delft, Faculty of Applied Sciences, Department of Radiation Science & Technology