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
{"title":"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","authors":"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","doi":"10.1007/s11243-024-00596-5","DOIUrl":null,"url":null,"abstract":"<div><p>Two new metal complexes containing the ligand thiobenzamide (TBz), with the formula <i>cis</i>-[RuCl(TBz)(L)<sub>2</sub>]PF<sub>6</sub>, where L = 2,2’-bipyridine (bpy) or o-phenanthroline (phen), were synthesized and characterized by cyclic voltammetry and spectroscopic techniques (UV–Vis, IR, <sup>1</sup>H and <sup>13</sup>C 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 IC<sub>50</sub> ranging from 1.5 µmol L<sup>−1</sup> to 5.7 µmol L<sup>−1</sup>. Interestingly, [RuCl(TBz)(bpy)<sub>2</sub>]PF<sub>6</sub> 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)<sub>2</sub>]PF<sub>6</sub> 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.</p></div>","PeriodicalId":803,"journal":{"name":"Transition Metal Chemistry","volume":"49 6","pages":"453 - 464"},"PeriodicalIF":1.6000,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Thiobenzamide-based ruthenium complexes: chemical reactivity and promising biological investigations against Leukemia cancer cells\",\"authors\":\"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\",\"doi\":\"10.1007/s11243-024-00596-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Two new metal complexes containing the ligand thiobenzamide (TBz), with the formula <i>cis</i>-[RuCl(TBz)(L)<sub>2</sub>]PF<sub>6</sub>, where L = 2,2’-bipyridine (bpy) or o-phenanthroline (phen), were synthesized and characterized by cyclic voltammetry and spectroscopic techniques (UV–Vis, IR, <sup>1</sup>H and <sup>13</sup>C 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 IC<sub>50</sub> ranging from 1.5 µmol L<sup>−1</sup> to 5.7 µmol L<sup>−1</sup>. Interestingly, [RuCl(TBz)(bpy)<sub>2</sub>]PF<sub>6</sub> 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)<sub>2</sub>]PF<sub>6</sub> 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.</p></div>\",\"PeriodicalId\":803,\"journal\":{\"name\":\"Transition Metal Chemistry\",\"volume\":\"49 6\",\"pages\":\"453 - 464\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transition Metal Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11243-024-00596-5\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transition Metal Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s11243-024-00596-5","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
Thiobenzamide-based ruthenium complexes: chemical reactivity and promising biological investigations against Leukemia cancer cells
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.
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.