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

IF 1.7 4区化学 Q3 CHEMISTRY, INORGANIC & NUCLEAR Transition Metal Chemistry 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

Transition Metal Chemistry 化学-无机化学与核化学

CiteScore

3.60

自引率

0.00%

发文量

审稿时长

1.3 months

期刊介绍： Transition Metal Chemistry is an international journal designed to deal with all aspects of the subject embodied in the title: the preparation of transition metal-based molecular compounds of all kinds (including complexes of the Group 12 elements), their structural, physical, kinetic, catalytic and biological properties, their use in chemical synthesis as well as their application in the widest context, their role in naturally occurring systems etc. Manuscripts submitted to the journal should be of broad appeal to the readership and for this reason, papers which are confined to more specialised studies such as the measurement of solution phase equilibria or thermal decomposition studies, or papers which include extensive material on f-block elements, or papers dealing with non-molecular materials, will not normally be considered for publication. Work describing new ligands or coordination geometries must provide sufficient evidence for the confident assignment of structural formulae; this will usually take the form of one or more X-ray crystal structures.