Half‐Sandwich p ‐Cymene Ruthenium (II) Complexes of N/S‐Donor Imine Ligands: Promising Chemotherapeutic Agent Against HCT116 Colon Cancer Cells

ABSTRACT Two half‐sandwich (η 6 ‐ p ‐cymene) ruthenium compounds, Ru‐CH₃L and Ru‐HL , have been prepared via metal–ligand coordination with ligands CH₃L and HL , respectively. The synthesized compounds were characterized by FT‐IR, 1 H NMR, 13 C NMR, and elemental analysis. The coordination of the ligand to Ru (II) via phenolic‐O and imine‐N atoms was proved by the single X‐ray structure of CH₃L , HL , and Ru‐CH₃L . Moreover, the interactions of Ru‐CH 3 L and Ru‐HL with HSA were also examined. Ru‐CH 3 L and Ru‐HL bind to HSA with moderate affinity and static binding mode. The cytotoxicity of the compounds against HCT116, Caco‐2, MCF‐7, and HUVECs was evaluated by the MTT test. Ru‐CH₃L showed potent activity against HCT116 cells with an IC₅₀ value of 18 μM. We have conducted comprehensive in vitro testing of Ru‐CH₃L against HCT116 cells. Treatment with Ru‐CH 3 L in HCT116 cells led to cell shrinkage, cell separation, increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (MMP), and activation of caspase‐3/7, culminating in cell apoptosis. Moreover, cell death and G2/M cell cycle arrest were observed.