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 ]PF 6 , where L = 2,2’-bipyridine (bpy) or o-phenanthroline (phen), were synthesized and characterized by cyclic voltammetry and spectroscopic techniques (UV–Vis, IR, 1 H and 13 C NMR). These com...

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Published in:Transition metal chemistry (Weinheim) 2024-12, Vol.49 (6), p.453-464
Main Authors: Azevedo, Paulo G. F., Pacheco, Luciano V., Carneiro, Felipe E. M., Fernandes, Gabriela C., de Sá, Denise S., Santos, Ivanilson P., Meira, Cássio S., Soares, Milena B. P., Paulo, Tércio F., Sousa, Eduardo H. S., Lopes, Luiz G. F., da Silva, Carlos D. S.
Format: Article
Language:English
Subjects:
Biological effects
Cancer
Catalysis
Chemistry
Chemistry and Materials Science
Combinatorial analysis
Coordination compounds
Depolarization
Doxorubicin
Inorganic Chemistry
Leukemia
NMR
Nuclear magnetic resonance
Organometallic Chemistry
Physical Chemistry
Ruthenium compounds
Synergistic effect
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Summary:Two new metal complexes containing the ligand thiobenzamide (TBz), with the formula cis -[RuCl(TBz)(L) 2 ]PF 6 , where L = 2,2’-bipyridine (bpy) or o-phenanthroline (phen), were synthesized and characterized by cyclic voltammetry and spectroscopic techniques (UV–Vis, IR, 1 H and 13 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 50 ranging from 1.5 µmol L −1 to 5.7 µmol L −1 . Interestingly, [RuCl(TBz)(bpy) 2 ]PF 6 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 ]PF 6 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.
ISSN:0340-4285
1572-901X
DOI:10.1007/s11243-024-00596-5