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Artificial chemical nuclease and cytotoxic activity of a mononuclear copper(I) complex and a related binuclear double-stranded helicate
European Journal of Inorganic Chemistry ( IF 2.3 ) Pub Date : 2021-09-12 , DOI: 10.1002/ejic.202100673
Pedro Levín 1 , Lucía M. Balsa 2 , Carlos P. Silva 3 , Austin E. Herzog 4 , Andrés Vega 5 , Jorge Pavez 1 , Ignacio E. León 2 , Luis Lemus 6
Affiliation  

Copper complexes are promising candidates for anticancer drugs, because of their redox properties and the ability to generate ROS (reactive oxygen species) in the cellular media. Most of the reported complexes with anticancer properties are based on Cu(II), which must be reduced to Cu(I) to exert the therapeutic action. Here, we report on the synthesis and characterization of two novel copper(I) complexes, a mononuclear complex [Cu(L1)2](ClO4) (1) and a binuclear helicate [Cu2(L2)2 ](ClO4) 2 (2) ( L1 = 2-ethoxy-1,10-phenanthroline, L2 = 1,2-bis((1,10-phenanthrolin-2-yl)oxy)ethane), which were designed to be structurally comparable, in order to evaluate the effect of nuclearity on the artificial nuclease activity. The activity of helicate (2) was higher than that of the monometallic (1) , and the DNA cleavage mechanism is through the generation of hydroxyl radical in a Fenton-like reaction, which occurs after oxidation of Cu(I) by O2 . Also, helicate (2) showed a higher cytotoxic effect against different cancer cells lines, while both complexes are more active than cisplatin.

中文翻译:

单核铜(I)复合物和相关双核双链螺旋的人工化学核酸酶和细胞毒活性

铜配合物是抗癌药物的有希望的候选物,因为它们具有氧化还原特性和在细胞介质中产生 ROS(活性氧)的能力。大多数报道的具有抗癌特性的配合物都基于 Cu(II),必须将其还原为 Cu(I) 才能发挥治疗作用。在这里,我们报告了两种新型铜 (I) 配合物的合成和表征,即单核配合物 [Cu(L1)2](ClO4) (1) 和双核螺旋体 [Cu2(L2)2 ](ClO4) 2 ( 2) (L1 = 2-ethoxy-1,10-phenanthroline, L2 = 1,2-bis((1,10-phenanthrolin-2-yl)oxy)ethane),它们被设计为在结构上具有可比性,以便评估核对人工核酸酶活性的影响。螺旋体(2)的活性高于单金属(1),DNA 裂解机制是通过在类芬顿反应中产生羟基自由基,该反应发生在 O2 氧化 Cu(I) 后。此外,helicate (2) 对不同的癌细胞系显示出更高的细胞毒性作用,而这两种复合物都比顺铂更具活性。
更新日期:2021-09-12
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