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乙酰化半乳糖吡喃基 N-杂环单卡宾银(I)配合物作为横纹肌肉瘤细胞系中新型的抗增殖剂。

Acetylated galactopyranosyl N-heterocyclic monocarbene complexes of Silver(I) as novel anti-proliferative agents in a rhabdomyosarcoma cell line.

机构信息

INQUISUR, Departamento de Química, Universidad Nacional del Sur (UNS-CONICET), 8000 Bahía Blanca, Argentina.

INBIOSUR (UNS-CONICET), Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, 8000 Bahía Blanca, Argentina; Comisión de Investigaciones Científicas de la provincia de Buenos Aires (CIC PBA), Argentina.

出版信息

Bioorg Med Chem. 2024 Jun 1;107:117756. doi: 10.1016/j.bmc.2024.117756. Epub 2024 May 11.

Abstract

Herein, four silver(I) complexes bearing acetylated d-galactopyranoside-based N-heterocyclic carbene ligands were synthesized and fully characterized by elemental analysis, NMR, and X-ray photoelectron spectroscopy. All complexes were obtained with an anomeric β-configuration and as monocarbene species. In this study, we investigated the biological effects of the silver(I) complexes 2a-d on the human rhabdomyosarcoma cell line, RD. Our results show concentration-dependent effects on cell density, growth inhibition, and activation of key signaling pathways such as Akt 1/2, ERK 1/2, and p38-MAPK, indicating their potential as anticancer agents. Notably, at 35.5 µM, the complexes induced mitochondrial network disruption, as observed with 2b and 2c, whereas with 2a, this disruption was accompanied by nuclear content release. These results provide insight into the utility of carbohydrate incorporated NHC complexes of silver(I) as new agents in cancer therapy.

摘要

本文合成了四个带有乙酰化半乳糖吡喃糖苷基 N-杂环卡宾配体的银(I)配合物,并通过元素分析、NMR 和 X 射线光电子能谱对其进行了全面表征。所有配合物均以端基β-构型和单卡宾形式获得。在这项研究中,我们研究了银(I)配合物 2a-d 对人横纹肌肉瘤细胞系 RD 的生物学效应。我们的结果表明,它们对细胞密度、生长抑制和 Akt 1/2、ERK 1/2 和 p38-MAPK 等关键信号通路的激活具有浓度依赖性效应,表明它们具有作为抗癌剂的潜力。值得注意的是,在 35.5µM 时,配合物 2b 和 2c 诱导线粒体网络破坏,而配合物 2a 则伴随着核内容物的释放。这些结果为将含碳水化合物的 NHC 银(I)配合物作为癌症治疗的新药物提供了深入了解。

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