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2',6'-二(噻唑-2-基)-2,4'-联吡啶的钯(II)和铂(II)配合物的细胞毒性:对细胞死亡模式和细胞周期阻滞的见解

Cytotoxicity of Pd(ii) and Pt(ii) complexes of 2',6'-di(thiazol-2-yl)-2,4'-bipyridine: insights into the mode of cell death and cell cycle arrest.

作者信息

Mansour Ahmed M, Radacki Krzysztof, Shehab Ola R, Mostafa Gamal A E, Ali Essam A, Abo-Elfadl Mahmoud T

机构信息

Department of Chemistry, United Arab Emirates University Al-Ain United Arab Emirates

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

出版信息

RSC Adv. 2025 Apr 16;15(16):12057-12066. doi: 10.1039/d5ra00647c.

Abstract

Square-planar complexes were synthesized by the reaction of 2',6'-di(thiazol-2-yl)-2,4'-bipyridine with either Na[PdCl] or K[PtCl], and these were thoroughly structurally characterized using some analytical and spectroscopic techniques. Density functional theory computations, including natural bond orbital analysis, were used to complement the experimental work to gain insight into the natural charge and electronic arrangement of the metal ion, as well as the strength of the metal-ligand bonds. The Pd(ii) complex exhibited exceptional cytotoxicity against the A549 and HCT-116 cell lines with IC values of 60.1 ± 3.45 and 23.8 ± 1.48 μM, respectively. Unfortunately, the Pd(ii) complex was harmful to the Vero normal cell line with an IC value of 24.5 ± 2.13 μM. The Pt(ii) complex is unstable and has a high likelihood of exchanging the chlorido ligand for solvent molecules such as DMSO. The fluorescent-stain photos of the treated HCT-116 cells with the Pd(ii) complex showed increased apoptotic bodies, indicating both early (18%) and late apoptosis (32%), as well as a necrosis ratio of about 10%. Flow cytometric analysis demonstrated that a cell arrest was induced by the Pd(ii) complex on HCT-116 cells in the G/M phase.

摘要

通过2',6'-二(噻唑-2-基)-2,4'-联吡啶与Na[PdCl]或K[PtCl]反应合成了平面正方形配合物,并使用一些分析和光谱技术对其进行了全面的结构表征。密度泛函理论计算,包括自然键轨道分析,被用于补充实验工作,以深入了解金属离子的自然电荷和电子排布,以及金属-配体键的强度。Pd(ii)配合物对A549和HCT-116细胞系表现出优异的细胞毒性,IC值分别为60.1±3.45和23.8±1.48μM。不幸的是,Pd(ii)配合物对Vero正常细胞系有害,IC值为24.5±2.13μM。Pt(ii)配合物不稳定,很可能将氯配体交换为溶剂分子,如DMSO。用Pd(ii)配合物处理的HCT-116细胞的荧光染色照片显示凋亡小体增加,表明早期凋亡(18%)和晚期凋亡(32%)均有增加,坏死率约为10%。流式细胞术分析表明,Pd(ii)配合物诱导HCT-116细胞在G/M期发生细胞阻滞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a6/12001024/999c4db47c40/d5ra00647c-f1.jpg

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