Aim:
This study aimed to synthesize and characterize a series of salicylaldehyde semicarbazones and their Cu(II) complexes, and to investigate their cytotoxic activities and mechanisms of action against human tumor cell lines.
Methods:
Using QSAR studies as a guide, ligands of the general formula HOC₆H₄CH=N–NHCONR₂ (H₂R₂) and their corresponding Cu(II) complexes were synthesized and characterized. Their cytotoxic activities were assessed against various human tumor cell lines. Further biochemical and apoptotic assays were conducted on two promising complexes, [Cu(HBnz₂)Cl] and [Cu(HBu₂)Cl], followed by proteomic analyses to study changes in protein expression profiles associated with their cytotoxic mechanisms.
Results:
The Cu(II) complexes exhibited enhanced cytotoxicity compared to their free ligands. Apoptotic assays indicated that [Cu(HBnz₂)Cl] and [Cu(HBu₂)Cl] mediated cell death in MOLT-4 cells through apoptosis. Proteomic investigations revealed distinct alterations in protein expression profiles, suggesting pathways involved in the compounds' modes of action.
Conclusion:
Complexation of salicylaldehyde semicarbazones with Cu(II) enhances their cytotoxic activities, with apoptosis identified as a primary mechanism of action in MOLT-4 cells. Proteomic analysis provided further insights into the molecular pathways underlying their cytotoxic effects.