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基于二苯甲酰甲烷银(I)配合物的实验与计算研究、与DNA/RNA/牛血清白蛋白生物分子的相互作用及体外细胞毒性活性。

Experimental and computational studies of silver(I) dibenzoylmethane-based complexes, interaction with DNA/RNA/BSA biomolecules, and in vitro cytotoxic activity.

作者信息

Elsayed Shadia A, Saleh Elham E, Aboelnga Mohamed M, Toson Elshahat A

机构信息

Chemistry Department, Faculty of Science, Damietta University, New Damietta 34517, Egypt.

Chemistry Department, Faculty of Science, Damietta University, New Damietta 34517, Egypt.

出版信息

J Inorg Biochem. 2023 Apr;241:112132. doi: 10.1016/j.jinorgbio.2023.112132. Epub 2023 Jan 20.

DOI:10.1016/j.jinorgbio.2023.112132
PMID:36701985
Abstract

Two silver(I) complexes of composition [Ag(L)] (1) and Ag(L)(PPh) (HL = dibenzoyl- methane, PPh = triphenylphosphine) were synthesized and characterized by elemental analysis, FTIR, NMR, XRPD, and UV-visible spectra. The molecular structures of the studied ligands and Ag(I) complexes have been characterized using Density Function Theory (DFT) calculations. This analysis has enabled us to determine the reactivity and the coordination site(s) for each ligand. Ag(I) ion is found to be coordinated with the ligand's oxygens in almost a linear fashion in complex (1), while in complex (2) it adopts a tetrahedral geometry. The interaction compounds with biomolecules; calf thymus (ct DNA), yeast-tRNA, and bovine serum albumin (BSA) were investigated using both absorption and fluorescence spectroscopy. The in vitro cytotoxic studies of the complexes against normal human lung fibroblast (WI38), cancerous breast (MDA-MB-231), mammary gland breast (MCF7), hepatocellular (HePG2), and prostate (PC3) cell lines indicated that the complexes are highly toxic to the cancer cells but less toxic towards the normal one when compared with the ligand. Flow cytometric results showed that complex (1) induced cell cycle arrest at the G2/M phase, and complex (2) at G2/M and S phases. Moreover, the results of apoptotic genes (caspase3 and p53) and anti-apoptotic (Bcl2) led us to suggest an apoptotic killing mechanism of cells rather than a necrotic one.

摘要

合成了两种组成为[Ag(L)] (1) 和[Ag(L)(PPh)] (2) 的银(I)配合物(HL = 二苯甲酰甲烷,PPh = 三苯基膦),并通过元素分析、傅里叶变换红外光谱(FTIR)、核磁共振(NMR)、X射线粉末衍射(XRPD)和紫外可见光谱对其进行了表征。使用密度泛函理论(DFT)计算对所研究的配体和Ag(I)配合物的分子结构进行了表征。该分析使我们能够确定每种配体的反应活性和配位位点。发现Ag(I)离子在配合物(1)中几乎以线性方式与配体的氧原子配位,而在配合物(2)中它采用四面体几何构型。使用吸收光谱和荧光光谱研究了与生物分子;小牛胸腺(ct DNA)、酵母tRNA和牛血清白蛋白(BSA)的相互作用化合物。对这些配合物针对正常人肺成纤维细胞(WI38)、癌性乳腺(MDA-MB-231)、乳腺(MCF7)、肝细胞(HePG2)和前列腺(PC3)细胞系的体外细胞毒性研究表明,与配体相比,这些配合物对癌细胞具有高毒性,但对正常细胞毒性较小。流式细胞术结果表明,配合物(1)诱导细胞周期停滞在G2/M期,配合物(2)诱导细胞周期停滞在G2/M期和S期。此外,凋亡基因(caspase3和p53)和抗凋亡(Bcl2)的结果使我们提出细胞的凋亡杀伤机制而非坏死机制。

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