In vitro and in vivo studies of a decanuclear Ni(II) complex as a potential anti-breast cancer agent.

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-11-10 DOI:10.1016/j.bioorg.2024.107949

Haitao Zhu, Houcong Li, Yuxin Ji, Min Hou, Qingling Yang, Lili Liang, Wenge Li

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Abstract

A non-platinum-metal decanuclear complex [Ni₁₀L₄(CH₃COO)₈ (C₂H₅OH)₈]·8(C₂H₅OH) (Ni₁₀ complex) has been developed with a tri-dentate 2,3-dihydroxybenzaldehyde-2-aminophenol Schiff base ligand (H₃L). Single crystal X-ray analysis reveals that the Ni₁₀ complex displays a sandwich loaf-shaped decanuclear structure and its anticancer activity was evaluated. The cell cytotoxicity results indicating that the Ni₁₀ complex is most effective to human breast cancer cells MDA-MB-231 and its mechanism were further investigated. Flow cytometry analysis showed that the Ni₁₀ complex triggered cell cycle arrest and induced apoptosis of MDA-MB-231 cells. Western blot analysis of the changes of intracellular protein expression showed that Ni₁₀ triggers MDA-MB-231 apoptosis through mitochondrial mediated apoptosis signaling pathways. In vivo experiments showed that the Ni₁₀ complex significantly suppressed breast tumor growth with low toxicity against major organs in a nude mice model. The good treatment effect, low toxicity and pharmacological mechanisms of the decanuclear Ni^II complex may provide a clue for the research and development of non-platinum multinuclear based chemotherapeutic drugs.

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十核 Ni(II) 复合物作为潜在抗乳腺癌药物的体外和体内研究。

一种非铂金属十核络合物[Ni10L4(CH3COO)8 (C2H5OH)8]-8(C2H5OH)（Ni10络合物）以三位 2,3-二羟基苯甲醛-2-氨基苯酚席夫碱配体（H3L）研制成功。单晶 X 射线分析表明，Ni10 复合物显示出夹心面包状十核结构，并对其抗癌活性进行了评估。细胞毒性结果表明，Ni10 复合物对人类乳腺癌细胞 MDA-MB-231 最有效，并对其机理进行了进一步研究。流式细胞术分析表明，Ni10 复合物能引发 MDA-MB-231 细胞周期停滞和凋亡。对细胞内蛋白表达变化的 Western 印迹分析表明，Ni10 通过线粒体介导的凋亡信号通路触发 MDA-MB-231 细胞凋亡。体内实验表明，在裸鼠模型中，Ni10 复合物能显著抑制乳腺肿瘤的生长，且对主要器官毒性较低。十核 NiII 复合物的良好治疗效果、低毒性和药理机制，为非铂多核化疗药物的研发提供了线索。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.