Siloxane-spaced salen-type Schiff base cobalt complex. Experimental and docking analysis—a dual approach for evaluating anti-cancer efficacy

A complex of Co(II), <b>CoL¹</b> , with a salen-type Schiff base ligand, <b>H₂L¹</b> , having a siloxane spacer, was evaluated from the perspective of anti-cancer activity in comparison with a newly synthesized homologue under similar conditions, <b>CoL²</b> , but with a ligand with hexamethylene bridge, <b>H₂L²</b> . Molecular docking simulations were used to estimate the possible interactions of the two cobalt complexes and their parent ligands with some key proteins involved in cancer development, the results indicating that the silicon derivatives are more potent anti-tumours. This is attributed to the conformational flexibility of the siloxane segment that favours establishing interactions with biological targets. Cytotoxicity assays against two cancer cell lines (MCF-7 and HeLa) also demonstrated significantly higher activity and selectivity for the siloxane-containing complex <b>CoL¹,</b> compared with its fully organic ligand-based counterpart. The cytotoxicity of this complex on MCF-7 cell line showed a considerable effect at IC₅₀ of 22.61 μM, compared with the one shown by <b>CoL²</b> of 43.82 μM. The dual experimental and theoretical approach provides valuable insights into the potential of designing Schiff base complexes with optimized therapeutic profiles and highlights the importance of the silicon structural motif in improving the efficacy of metal-based anti-tumour agents.