New dinuclear gold(III) complex with 1,5-naphthyridine as bridging ligand: synthesis, characterization, DNA/BSA binding studies, and anticancer activity

IF 2.1 4区 工程技术 Q3 CHEMISTRY, INORGANIC & NUCLEAR Gold Bulletin Pub Date : 2024-04-12 DOI:10.1007/s13404-024-00344-8
Snežana Radisavljević, Dušan Ćoćić, Biljana Petrović, Ina Kellner, Ivana Ivanović-Burmazović, Nikola Radenković, Danijela Nikodijević, Milena Milutinović
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Abstract

To elucidate an antitumor drug exhibiting enhanced activity relative to cisplatin, a novel dinuclear gold(III) complex was synthesized, incorporating 1,5-naphthyridine as a bridging ligand. Subsequently, the newly synthesized complex underwent comprehensive characterization using various techniques to validate its structural attributes. The stability of the complex in both water and PBS buffer was assessed through UV–Vis spectroscopy. DNA binding studies were conducted employing UV–Vis, fluorescence spectroscopy, and viscosity measurements. Competitive studies with ethidium bromide (EB) or 4′-hydroxyethidium (HOE) were performed utilizing fluorescence spectroscopy. The findings indicated that the dinuclear gold(III) complex interacts with calf thymus DNA (CT-DNA) through a groove binding mode. Moreover, the investigated complex exhibited significant binding constants for its interaction with human serum albumin (HSA) and bovine serum albumin (BSA) and interactions in the presence of site markers (eosin Y or ibuprofen). The dinuclear gold(III) complex demonstrated notable cytotoxicity against HCT116 and MDA-MB-231 cancer cell lines at 24 and 72 h post-treatment. Furthermore, the complex displayed selectivity by inducing significantly lower cytotoxic activity in healthy cells than in cancerous ones. In support of its antitumor activity, the complex exhibited proapoptotic effects, as evidenced by increased caspase 9 activity and low percentages of necrosis. Molecular docking simulations were employed to corroborate all experimentally obtained results.

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以 1,5-萘啶为桥接配体的新型双核金(III)配合物:合成、表征、DNA/BSA 结合研究和抗癌活性
为了阐明一种比顺铂具有更强活性的抗肿瘤药物,我们合成了一种新型双核金(III)配合物,并将 1,5萘啶作为桥接配体。随后,利用各种技术对新合成的配合物进行了全面表征,以验证其结构属性。通过紫外可见光谱评估了复合物在水和 PBS 缓冲液中的稳定性。利用紫外可见光谱、荧光光谱和粘度测量进行了 DNA 结合研究。利用荧光光谱与溴化乙锭(EB)或 4′-羟基乙锭(HOE)进行了竞争研究。研究结果表明,双核金(III)配合物通过沟结合模式与小牛胸腺 DNA(CT-DNA)相互作用。此外,所研究的复合物在与人血清白蛋白(HSA)和牛血清白蛋白(BSA)的相互作用中,以及在存在位点标记物(伊红 Y 或布洛芬)的情况下的相互作用中,均表现出显著的结合常数。处理后 24 小时和 72 小时,双核金(III)复合物对 HCT116 和 MDA-MB-231 癌细胞株具有显著的细胞毒性。此外,该复合物还具有选择性,对健康细胞的细胞毒性活性明显低于对癌细胞的毒性活性。为了支持其抗肿瘤活性,该复合物还表现出促进细胞凋亡的作用,这体现在 caspase 9 活性的增加和较低的坏死率上。分子对接模拟证实了所有实验结果。
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来源期刊
Gold Bulletin
Gold Bulletin Chemistry-Inorganic Chemistry
CiteScore
3.70
自引率
4.50%
发文量
21
期刊介绍: Gold Bulletin is the premier international peer reviewed journal on the latest science, technology and applications of gold. It includes papers on the latest research advances, state-of-the-art reviews, conference reports, book reviews and highlights of patents and scientific literature. Gold Bulletin does not publish manuscripts covering the snthesis of Gold nanoparticles in the presence of plant extracts or other nature-derived extracts. Gold Bulletin has been published over 40 years as a multidisciplinary journal read by chemists, physicists, engineers, metallurgists, materials scientists, biotechnologists, surface scientists, and nanotechnologists amongst others, both within industry and academia. Gold Bulletin is published in Association with the World Gold Council.
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