Thiobenzamide-based ruthenium complexes: chemical reactivity and promising biological investigations against Leukemia cancer cells

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-07-06 DOI:10.1007/s11243-024-00596-5

Paulo G. F. Azevedo, Luciano V. Pacheco, Felipe E. M. Carneiro, Gabriela C. Fernandes, Denise S. de Sá, Ivanilson P. Santos, Cássio S. Meira, Milena B. P. Soares, Tércio F. Paulo, Eduardo H. S. Sousa, Luiz G. F. Lopes, Carlos D. S. da Silva

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Abstract

Two new metal complexes containing the ligand thiobenzamide (TBz), with the formula cis-[RuCl(TBz)(L)₂]PF₆, where L = 2,2’-bipyridine (bpy) or o-phenanthroline (phen), were synthesized and characterized by cyclic voltammetry and spectroscopic techniques (UV–Vis, IR, ¹H and ¹³C NMR). These compounds showed cytotoxic activity in all cancer cell lines studied. The HL-60 strain was the most sensitive to both metal complexes, with IC₅₀ ranging from 1.5 µmol L⁻¹ to 5.7 µmol L⁻¹. Interestingly, [RuCl(TBz)(bpy)₂]PF₆ exhibited a significant selectivity index of 6.6 for the cytotoxicity ratio between normal cells (MRC-5) and cancer cells (HL-60). In addition, this metal complex promoted mitochondrial membrane depolarization and increased mitochondrial superoxide production. Finally, synergism was observed between [RuCl(TBz)(bpy)₂]PF₆ and doxorubicin in combination against a cell model with HL-60 cells. A combinatorial index of 0.27 was observed in this study. In addition, an isobologram study showed points below the isobolographic line, indicating a synergistic effect. These results show promising pharmacological potential for these compounds which deserve further biological investigation.

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硫代苯甲酰胺基钌配合物：针对白血病癌细胞的化学反应活性和前景广阔的生物学研究

通过循环伏安法和光谱技术（紫外-可见光谱、红外光谱、1H 和 13C NMR），合成了两种含有配体硫代苯甲酰胺（TBz）的新金属配合物，其化学式为顺式-[RuCl(TBz)(L)2]PF6，其中 L = 2,2'- 联吡啶 (bpy) 或邻菲罗啉 (phen)。这些化合物在研究的所有癌细胞系中都显示出细胞毒性活性。HL-60 株系对这两种金属复合物最为敏感，其 IC50 为 1.5 µmol L-1 至 5.7 µmol L-1。有趣的是，[RuCl(TBz)(bpy)2]PF6 在正常细胞（MRC-5）和癌细胞（HL-60）之间的细胞毒性比值显示出 6.6 的显著选择性指数。此外，这种金属复合物还能促进线粒体膜去极化，增加线粒体超氧化物的产生。最后，[RuCl(TBz)(苄基)2]PF6 与多柔比星的组合对 HL-60 细胞模型产生了协同作用。这项研究观察到的组合指数为 0.27。此外，一项等全息图研究显示了低于等全息线的点，表明存在协同效应。这些结果表明这些化合物具有良好的药理潜力，值得进一步进行生物学研究。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.