The doi above is for this specific version of this dataset, which is currently the latest. Newer versions may be published in the future. For a link that will always point to the latest version, please use
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

Dataset

• Organic Chemistry
• Chemical Sciences

chemotherapy, prodrug, radiation chemistry, radiotherapy, self-immolative linker

2021-2024

CC0

RefWorks, BibTeX, Reference Manager, Endnote, DataCite, NLM, DC, CFF

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.

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

4TU.ResearchData

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

• China Scholarship Council (CSC)

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