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