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":"<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>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"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\":\"<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>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-07-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11243-024-00596-5\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11243-024-00596-5","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","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：
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.
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