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Three new dicyanidoaurate(I)-based complexes exhibiting significant antiproliferative property: synthesis and characterization
Gold Bulletin ( IF 2.1 ) Pub Date : 2019-01-03 , DOI: 10.1007/s13404-018-00251-9
Ali Aydın , Ahmet Karadağ , Şaban Tekin , Hüseyin Akbaş

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.

中文翻译:

三种具有显着抗增殖特性的新型双氰基金酸盐(I)复合物:合成与表征

Au(CN)2- 离子及其金属配体化合物最近在工业应用中引起了极大的兴趣,例如光学诊断系统以及具有抗风湿和抗肿瘤活性的药理学。这里,[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)和[Zn2(μ-N-bishydetenH)(N-bishydeten)(NC)2Au][Au(CN)2](C3)通过反应合成金属盐与 N,N-双(2-羟乙基)乙二胺 (N-bisyhdeten) 和 K[Au(CN)2]。使用元素分析和 FT-IR 对 Au(I) 化合物进行了表征。还测试了 ESI-MS 和热测量技术及其药理特性。这些化合物的 DNA/牛血清白蛋白 (BSA) 相互作用通过分光光度法滴定、荧光溴化乙锭动力学、和 DNA 电泳研究,并测定了这些化合物在生理溶液中的稳定性。研究结果表明,这些化合物表现出与顺铂相似的 DNA/BSA 结合活性,并表现出很强的水性稳定性。Au(I) 化合物是有效的抗增殖剂,具有低坏死活性,并表现出剂量依赖性的癌细胞生长抑制作用,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 的减少可能是细胞凋亡效应的主要原因,例如 DNA 断裂和核塌陷。关于 Au(I) 化合物对细胞的作用方式的研究表明,它们会降低细胞迁移率和细胞骨架蛋白(即 CK7 和 CK20)的水平。在这个证据的基础上,
更新日期:2019-01-03
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