在结构,协调和抗癌活动的黄金 (I/III) 双氨酸复合物的固体测量效应
Adedamola S Arojojoye1, Justin Holmes1, Oluwatosin A Obisesan1
1Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA. awuah@uky.edu.
Dalton transactions (Cambridge, England : 2003)
|December 17, 2024
概括
合成具有相同连接体框架的金 (I) 和金 (III) 复合体揭示了不同的抗癌机制. 黄金 (III) 复合物诱导氧化应激和线粒体功能障碍,提供新的治疗策略.
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:
- 了解黄金氧化状态 (Au(I) 与黄金氧化状态 (Au(I) 的影响. 对于药物开发来说,对复杂功能的影响至关重要.
- 合成具有相同连接体系统的Au (I) 和Au (III) 复合体,由于前体的反应性和稳定性,因此存在重大挑战.
- 之前的研究仅限于直接比较同一分子框架内不同黄金氧化状态的生物效应.
研究的目的:
- 开发一种合成策略,用于制备结构上不同的黄金 (I) 和黄金 (III) 复合物,使用保存的连接体框架.
- 研究黄金氧化状态对复杂几何,生物活动和细胞机制的影响.
- 在相关的癌细胞系中比较Au (I) 和Au (III) 复合物的抗癌疗效和作用模式.
主要方法:
- 通过1,2-bis(diphenylphosphino) benzene与黄金前体 (HAuCl4·3H2O或AuCl3(tht)) 在不同的立体比率中反应合成黄金复合物.
- 使用高分辨率质谱 (HRMS),RP-HPLC-MS,核磁共振 (NMR) 谱学 (特别是31P NMR) 和元素分析进行表征.
- 通过X射线晶体学阐明Au(III) 复合物的结构.
- 对MDA-MB-231 (乳腺癌) 和BT-333 (质母细胞瘤) 细胞系的抗癌活性的评估.
- 评估线粒体呼吸抑制,反应性氧物种 (ROS) 积累和线粒体膜潜在脱极化.
主要成果:
- 成功合成了具有1,2-bis-diphenylphosphino-benzene连接体的明显的阴阳性黄金 (I) 和黄金 (III) 复合体.
- 光谱数据 (31P NMR) 清楚地区分了Au (I) (∼22 ppm) 和Au (III) (∼57 ppm) 复合体.
- X射线结晶学证实了Au (III) 复合体的5坐标几何.
- 两种Au (I) 和Au (III) 复合体都表现出抗癌活性,并抑制了线粒体呼吸.
- 在MDA-MB-231细胞中,Au(III) 复合物独特诱导了ROS积累和线粒体膜脱极化.
结论:
- 开发的合成方法使得用相同的配体制备黄金 (I) 和黄金 (III) 复合物成为可能,从而便于直接比较它们的特性.
- 黄金的氧化状态显著影响复杂的几何和生物作用机制.
- 黄金 (III) 复合物表现出更强大的诱导氧化应激和线粒体损伤的能力,与黄金 (I) 复合物相比,这表明其具有明显的治疗潜力.
- 这项研究为了解黄金基抗癌剂的结构-活性关系提供了宝贵的平台.
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