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含2-(吡啶-2-基)喹喔啉的钌(II)羰基配合物的可见光诱导一氧化碳释放特性及细胞毒性

Visible-light-induced CO-releasing properties and cytotoxicity of a Ru(II) carbonyl complex containing 2-(pyridin-2-yl)-quinoxaline.

作者信息

Khaled Rabaa M, Abo-Elfadl Mahmoud T, Radacki Krzysztof, Abo Zeid Mona A M, Shehab Ola R, Abdel-Kader Nora S, Mostafa Gamal A E, Ali Essam A, Al Neyadi Shaikha S, Mansour Ahmed M

机构信息

Department of Chemistry, Faculty of Science, Cairo University, Gamma Street, Giza, Cairo 12613, Egypt.

Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza 12622, Egypt.

出版信息

Dalton Trans. 2025 Feb 4;54(6):2529-2539. doi: 10.1039/d4dt03082f.

Abstract

The photo-induced CO-releasing properties of the dark-stable complex [RuCl(CO)L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence and absence of biomolecules such as histidine, calf thymus DNA and hen egg white lysozyme. The CO release kinetics were consistent regardless of the presence of these biomolecules, suggesting that they did not influence the CO release mechanism. The quinoxaline ligand demonstrated exceptional cytotoxicity against human acute monocytic leukemia cells (THP-1), with evidence of potential DNA damage ascertained by comet assay, while it remained non-toxic to normal kidney epithelial cells derived from African green monkey (Vero) cell lines. In contrast, upon light activation, the Ru(II) complex showed no toxicity against THP-1 cells but was detrimental to Vero cells. In human colorectal carcinoma (HCT-116) cells, the ligand and the Ru(II) complex produced ROS under light and dark conditions. However, HCT-116 cells retained their ability to consume oxygen and produce ATP following CO treatment, suggesting that the ROS levels were insufficient to cause significant cellular damage. Morphological features of apoptosis, including apoptotic bodies, chromatin condensation, cell shrinkage, and membrane leakage, were observed in the presence of both the ligand and its complex, irrespective of light exposure.

摘要

在有和没有生物分子(如组氨酸、小牛胸腺DNA和鸡蛋清溶菌酶)存在的情况下,研究了暗稳定配合物[RuCl(CO)L](L = 2-(吡啶-2-基)喹喔啉)在468 nm光照下的光诱导CO释放特性。无论这些生物分子是否存在,CO释放动力学都是一致的,这表明它们不影响CO释放机制。喹喔啉配体对人急性单核细胞白血病细胞(THP-1)表现出异常的细胞毒性,彗星试验确定有潜在DNA损伤的证据,而对源自非洲绿猴(Vero)细胞系的正常肾上皮细胞仍无毒性。相比之下,光激活后,Ru(II)配合物对THP-1细胞没有毒性,但对Vero细胞有害。在人结肠直肠癌(HCT-116)细胞中,配体和Ru(II)配合物在光照和黑暗条件下都会产生活性氧。然而,CO处理后,HCT-116细胞仍保留消耗氧气和产生ATP的能力,这表明活性氧水平不足以造成显著的细胞损伤。无论光照与否,在配体及其配合物存在的情况下,都观察到了凋亡的形态学特征,包括凋亡小体、染色质浓缩、细胞收缩和膜渗漏。

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