IN VITRO MODULATION OF CELLULAR REDOX HOMEOSTASIS BY Cu-THIOSEMICARBAZONE COORDINATION COMPOUNDS

Rezumat

Objectives. Cellular redox homeostasis maintains the balance between oxidative and reductive processes and regulates key intracellular biochemical reactions. This homeostasis, together with the equilibrium of the glutathione system, is critical for cellular function and protection against oxidative stress (OS). In this manuscript, glutathione parameters are reported as total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (glutathione disulfide, GSSG), and the GSH/GSSG ratio. Cu-thiosemicarbazone coordination compounds have been reported to modulate these mechanisms. However, their comparative efficacy remains insufficiently investigated. The aim of this study was to evaluate the structural and dose-dependent effects of Cu-thiosemicarbazone coordination compounds on these glutathione-related parameters.

Methods. The in vitro impact of Cu-thiosemicarbazone coordination compounds on glutathione metabolism parameters was investigated at two different concentrations: 10.0 µmol/L and 1.0 µmol/L. The results were compared with a negative control, while doxorubicin (DOXO) was used as a positive control.

Results. The tested series included benzothiazole derivatives (CMA-18, CMD-8, MG-22), phenyl derivatives (CMC-34, CMJ-33, CMT-67), and allyl derivatives (CMG-41, TIA-123, TIA-160). CMA-18 and CMC-34 significantly diminished tGSH and GSSG while enhancing the GSH/GSSG ratio (p<0.05), indicating marked redox-modulating activity rather than a uniform antioxidant response. CMT-67 and MG-22 exhibited moderate effects, maintaining redox equilibrium at 1.0 µmol/L, whereas allyl Cu-thiosemicarbazones showed dose-dependent effects. DOXO slightly increased tGSH, GSH, and GSSG without major disturbances in the GSH/GSSG ratio.

Conclusions. The effects on glutathione metabolism were strongly influenced by both the structure and concentration of thiosemicarbazones. Phenyl and benzothiazole Cu-thiosemicarbazones pronounced redox-modulating effects, whereas CMT-67, MG-22, and allyl derivatives demonstrated more moderate or concentration-dependent responses. Because some compounds simultaneously reduced tGSH while increasing the GSH/GSSG ratio, these effects should be interpreted cautiously. The findings suggest that careful selection of chemical class and concentration may optimize redox modulation, with potential implications for the development of therapeutic agents targeting OS.