三种新的具有显著抗增殖特性的双氰胺酸酯配合物的合成和表征

IF 2.1 4区 工程技术 Q3 CHEMISTRY, INORGANIC & NUCLEAR
Ali Aydın, Ahmet Karadağ, Şaban Tekin, Hüseyin Akbaş
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引用次数: 1

摘要

非盟(CN) 2 ?离子及其金属配体化合物最近在光学诊断系统以及具有抗风湿和抗肿瘤活性的药理学等工业应用中获得了相当大的兴趣。本文用金属盐与N、N-双(2-羟基乙基)乙二胺(N-双乙基)和K[Au(CN)2]反应合成了[Ni2(N-双乙二胺)2][Au(CN)2]3[Au(CN)2]·H2O (C1)、[Cu2(N-双乙二胺)2][Au(CN)2]·H2O (C2)和[Zn2(μ-N-双乙二胺)(N-双乙二胺)(NC)2Au][Au(CN)2] (C3)。采用元素分析和红外光谱对Au(I)化合物进行了表征。并对ESI-MS和热测量技术及其药理学性质进行了测试。通过分光光度滴定、溴化乙啶荧光动力学和DNA电泳研究证明了这些化合物的DNA/牛血清白蛋白(BSA)相互作用,并确定了这些化合物在生理溶液中的稳定性。结果表明,这些化合物具有与顺铂相似的DNA/ bsa结合活性,并具有较强的水稳定性。Au(I)化合物是有效的抗增殖剂,具有低坏死活性,对癌细胞具有剂量依赖性的生长抑制作用,IC50值为0.12 ~ 0.73 μM。暴露于Au(I)化合物的细胞中p53的积累和Bcl-2的减少可能是凋亡效应的主要原因,如DNA断裂和核崩溃。关于Au(I)化合物对细胞的作用方式的研究表明,它们可以降低细胞迁移率和细胞骨架蛋白CK7和CK20的水平。基于这一证据,我们认为金(I)化合物具有较强的抗增殖活性,低坏死作用和微摩尔剂量范围,使其适合作为结肠癌和宫颈癌化疗药物进行进一步的药理学评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Three new dicyanidoaurate(I)-based complexes exhibiting significant antiproliferative property: synthesis and characterization

Three new dicyanidoaurate(I)-based complexes exhibiting significant antiproliferative property: synthesis and characterization

The Au(CN)2? ion and its metal-ligand compounds have recently gained considerable interest in industrial applications such as optical diagnostics systems as well as pharmacology with antirheumatic and antitumor activity. Here, [Ni2(N-bishydeten)2][Au(μ-CN)2]3[Au(CN)2]·H2O (C1), [Cu2(N-bishydeten)2][Au(μ-CN)2]3[Au(CN)2]·H2O (C2), and [Zn2(μ-N-bishydetenH)(N-bishydeten)(NC)2Au][Au(CN)2] (C3) were synthesized by reaction of the metal salts with N,N-bis(2-hydroxyethyl)ethylenediamine (N-bisyhdeten) and K[Au(CN)2]. The Au(I) compounds were characterized using elemental analysis and FT-IR. ESI-MS and thermal measurement techniques and their pharmacological properties were also tested. The DNA/bovine serum albumin (BSA) interactions of these compounds were demonstrated by spectrophotometric titration, fluorometric ethidium bromide kinetics, and DNA electrophoresis studies, and the stability of these compounds in physiological solution was also determined. The findings indicate that these compounds displayed a DNA/BSA-binding activity similar to that of cisplatin and exhibited a strong aqueous stability. The Au(I) compounds were potent antiproliferative agents with low necrotic activity and exhibited dose-dependent growth inhibition of cancer cells with IC50 value of 0.12–0.73?μM. Accumulation of p53 and decrease in Bcl-2 in cells exposed to Au(I) compounds may be the main causes for apoptotic effects, such as DNA fragmentation and nuclear collapse. Investigations regarding the mode of action of Au(I) compounds on cells revealed that they reduce the cell migration rate and the level of cytoskeletal proteins, namely CK7 and CK20. On the basis of this evidence, we suggest that strong antiproliferative activity, low necrotic effect, and micromolar dose range observed for Au(I) compounds make them suitable candidates for further pharmacological evaluation as chemotherapeutic agents in colon and cervix cancer.

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来源期刊
Gold Bulletin
Gold Bulletin Chemistry-Inorganic Chemistry
CiteScore
3.70
自引率
4.50%
发文量
21
期刊介绍: Gold Bulletin is the premier international peer reviewed journal on the latest science, technology and applications of gold. It includes papers on the latest research advances, state-of-the-art reviews, conference reports, book reviews and highlights of patents and scientific literature. Gold Bulletin does not publish manuscripts covering the snthesis of Gold nanoparticles in the presence of plant extracts or other nature-derived extracts. Gold Bulletin has been published over 40 years as a multidisciplinary journal read by chemists, physicists, engineers, metallurgists, materials scientists, biotechnologists, surface scientists, and nanotechnologists amongst others, both within industry and academia. Gold Bulletin is published in Association with the World Gold Council.
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