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Photoactivatable diazido Pt(IV) anticancer complex can bind to and oxidize all four nucleosides
Dalton Transactions ( IF 4 ) Pub Date : 2020-11-20 , DOI: 10.1039/d0dt03090b
Yiyu Cheng 1 , Jishuai Zhang , Kui Wu , Fang Gao , Yang Cheng , Tao Zou , Xiaoqin Wu , Yao Zhao , Fuyi Wang
Affiliation  

Photoactivatable diazidodihydroxido Pt(IV) complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1; py = pyridine) is a promising anticancer agent which can be activated by visible light to induce cancer cell death. DNA has been thought to be involved in the mechanism of action of this kind of Pt(IV) prodrug. However, the detailed photodecomposition pathways of complex 1 and its interaction modes with DNA are complex. Herein we report that upon light irradiation complex 1 can bind to all four nucleosides covalently with the reduced Pt(II) species. Moreover, apart from the covalent coordination, various oxidation adducts of these four nucleosides induced by the reactive oxidative species (ROS) generated during the photoactivation of the complex 1 have also been identified, especially the induced oxidation of adenosine and cytidine which was firstly reported for this kind of photoactivatable Pt(IV) prodrug. Such dual-action may contribute to the highly potent photo-antiproliferativity of complex 1 towards cancer cells, which may account for the unique mechanism of action of the photoactivatable diazido Pt(IV) anticancer complexes.

中文翻译:

可光活化的二叠氮铂 (IV) 抗癌复合物可以结合并氧化所有四种核苷

可光活化的二叠氮二氢氧化铂( IV )复合物反式反式反式-[Pt(N 3 ) 2 (OH) 2 (py) 2 ] ( 1 ; py = pyridine) 是一种很有前景的抗癌剂,可被可见光激活以诱导癌细胞死亡。DNA 被认为与这种 Pt( IV ) 前药的作用机制有关。然而,复合物1的详细光分解途径及其与 DNA 的相互作用模式是复杂的。在此我们报告说,在光照射下,复合物1可以与还原的 Pt 共价结合所有四种核苷(II ) 物种。此外,除了共价配位外,还鉴定了由复合物1光活化过程中产生的活性氧化物质 (ROS) 诱导的这四种核苷的各种氧化加合物,尤其是腺苷和胞苷的诱导氧化,这是首次报道的这种可光活化的 Pt( IV ) 前药。这种双重作用可能有助于复合物1对癌细胞的高效光抗增殖,这可能解释了可光活化的二叠氮 Pt( IV ) 抗癌复合物的独特作用机制。
更新日期:2020-11-27
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