铜 (II) 协调化合物基于2,6-甲基乙二二的bis-hydrazones:合成,结构和细胞毒性活性
Anna A Kapustina1, Yulia P Tupolova1, Leonid D Popov1
1Department of Chemistry, Southern Federal University, Rostov-on-Don, 344090, Russia. yptupolova@sfedu.ru.
Dalton transactions (Cambridge, England : 2003)
|January 23, 2024
概括
与西斯丁相比,新的含有异环接体的铜复合体显示出对肝癌细胞的抗癌活性增强. 这些复合物对健康的肺细胞具有较低的毒性,并与蛋白质强烈结合,其中一个复合物与DNA基相互作用.
科学领域:
- 协调化学 协调化学
- 药用化学 医学化学
- 材料科学 材料科学 材料科学
背景情况:
- 2,6-二甲基二二-氨酸是用于金属复合体合成的多功能联体.
- 铜复合物正在研究其潜在的治疗应用,包括抗癌活性.
- 了解结构-活性关系对于开发有效的抗癌药物至关重要.
研究的目的:
- 合成和描述新型铜 (II) 复合物与胺素,胺和含素的配体.
- 评估这些复合体对人类肝细胞癌 (HepG2) 和非瘤人类肺纤维细胞 (MRC-5) 细胞系的体外细胞毒性活性.
- 研究铜复合体与牛血清白蛋白 (BSA) 的结合相互作用及其与DNA相互作用的机制.
主要方法:
- 使用各种光谱技术 (NMR,IR,UV-vis,ESR) 和X射线衍射,合成和描述铜 (II) 复合物.
- 在HepG2和MRC-5细胞系的体外细胞毒性测定.
- 用于BSA结合研究的光光谱学和用于DNA相互作用机制的分子动力学模拟.
- 循环电压测量和X射线吸收光谱学用于结构和电子属性分析.
主要成果:
- 一系列具有扭曲的正方形-金字塔形和正方形-金字塔形几何形状的五坐标铜(II) 复合物成功合成.
- 合成的铜复合体显示出与西斯丁相比,对HepG2细胞的细胞毒性活性显著更高.
- 这些复合物对MRC-5细胞的毒性较低,对BSA.具有强烈的结合亲和力.
- 分子动力学模拟显示[Cu(HL) Cl]通过π堆叠与DNA基相互作用,主要与腺因和胆氨酸相互作用.
结论:
- 新型铜 (II) 复合物具有有前途的抗癌特性,具有有利的选择性.
- 强烈的结合BSA表明有潜在的向药物输送或改变的药物动力学特征.
- 鉴定的DNA相互作用机制为这些复合物的作用模式提供了洞察力.
- 这些发现支持这些铜复合物的发展,作为潜在的化疗剂.
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