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A New Class of Radiation-Activating Antitumor Prodrugs Releasing 5-Fluorodeoxyuridine: Synthesis, Reactivity and Biological Activity

机译:新型的释放5-氟脱氧尿苷的辐射激活抗肿瘤前药:合成,反应性和生物活性。

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摘要

A number of 3-substituted 5-fluorodeoxyuridine (5-FdUrd) derivatives (1-6) were synthesized to evaluate their radiation reactivity and biological activity as a new class of prodrugs that can be radiation-activated to release 5-FdUrd. The compounds 2-6 bearing substituents with a 2-oxo group underwent radiolytic reduction to release 5-FdUrd in considerably high yields under anoxic conditions, while the compound 1 without 2-oxo substituent was inactive in releasing 5-FdUrd. The cytotoxicities of 2-6 toward P388 T cells of mouse leukemia were less than 5-FdUrd, as indicated by an MTT assay. The apparent cytotoxicities were significantly enhanced by X-irradiation under hypoxic conditions. A conclusion was that 2-6 have no antitumor effect in contrast to 5-FdUrd, but can potentiate the effect of cancer radiotherapy by releasing a cell-killing component 5-FdUrd.
机译:合成了许多3-取代的5-氟脱氧尿苷(5-FdUrd)衍生物(1-6),以评估其辐射反应性和生物活性,作为可以被辐射激活释放5-FdUrd的新型前药。带有2-氧代基的取代基的化合物2-6在缺氧条件下进行辐射还原,以相当高的产率释放5-FdUrd,而没有2-氧代取代基的化合物1不具有释放5-FdUrd的活性。如MTT测定所表明的,2-6对小鼠白血病的P388T细胞的细胞毒性小于5-FdUrd。在缺氧条件下通过X射线辐照可以明显提高细胞的细胞毒性。结论是2-6与5-FdUrd相比没有抗肿瘤作用,但是可以通过释放细胞杀伤成分5-FdUrd来增强癌症放疗的效果。

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