Study of the decorporation efficacy and toxicity of tetradentate 3-hydroxy- 2-pyridinone ligands at the cellular level
Study of the decorporation efficacy and toxicity of tetradentate 3-hydroxy-2-pyridinone ligands at the cellular level作者机构：State Key Laboratory of Radiation Medicine and ProtectionSchool for Radiological and Interdisciplinary Sciences(RAD-X)Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou215123China Beijing Nuclear Industry Hospital-Fangshan CampusBeijing102413China
出 版 物：《Radiation Medicine and Protection》 (放射医学与防护（英文）)
年 卷 期：2020年第1卷第4期
页 面：159-165页
学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学]
基 金：We thank the National Natural Science Foundation of China(21790374,21771133,and 21976127) the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD) Jiangsu Post-doctoral Research Funding Program(7112850520)
主 题：Uranium Hydroxypyridinone Decorporation efficacy Cytotoxicity Metal complexation
摘 要：Objective:A series of experiments were carried out to study the comparative decorporation efficacy and toxicity of three tetradentate hydroxypyridinone ligands(3LI-1-Cm-3,2-HOPO,5LIO-1-Cm-3,2-HOPO,and 7LIO-1-Cm-3,2-HOPO)with the variation of the linker length and the ***:Three ligands were obtained from a 4-step synthesis via the amidation of HOPO unit and different *** titrations were carried out to evaluate the formation constants of their corresponding uranyl ***-8 and colony formation assays were used to compare the cytotoxicity of the three ligands and uranyl using renal proximal tubular epithelial(NRK-52E)*** vitro uranium removal assays were performed to assess decorporation efficiencies of those ligands by co-incubating uranium and chelators with NRK-52E cells for 48 ***:Among the three ligands,5LIO-1-Cm-3,2-HOPO exhibits the highest uranyl affinity(logβ110?18.6(7))in comparison to the other two ligands(logβ110?14.9(2)for 3LI-1-Cm-3,2-HOPO and logβ110?16.7(1)for 7LIO-1-Cm-3,2-HOPO).The results of CCK-8 tests and colony formation assays further elucidate that 5LIO-1-Cm-3,2-HOPO and 7LIO-1-Cm-3,2-HOPO both show a similar level of cytotoxicity compared with ZnNa3-DTPA at relatively low ligand *** contrast,in the 3LI-1-Cm-3,2-HOPO treated group,the cell viability decreased markedly with the increase of the ligand concentrations,and the colony formation capability of NRK-52E cells was ***,the comparative decorporation efficacy of the three ligands was obtained from in vitro uranium removal assays,suggesting that these ligands could significantly inhibit the cellular uptake and prompt the cellular release of uranium from NRK-52E cells by the level of 81.9%,91.8%,and 87.1%,***:Our current results demonstrate that the linker/backbone species would significantly affect the decorporation efficacy and toxicity of the tetradentate 3-hydroxy-2-pyridinone ligands
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