Ruthenium (II) complexes containing dehydroacetic acid and its imine derivative ligands. Synthesis, characterization and cancer cell growth anti-proliferation activity (GI₅₀) study

Two dehydroacetic acid (DHA, L₁H) related imine ligands, L₂H and L₃H were obtained in moderate yields by reacting DHA with 2,4,6-trimethylaniline and phenylhydrazine, respectively. Refluxing [Ru (η⁶-p-cymene)Cl₂]₂ with two equivalents of L₁Na, L₂H and L₃H in methanol generated ruthenium compounds [Ru (η⁶-p-cymene)Cl (L₁)] (1), [Ru (η⁶-p-cymene)Cl (L₂)] (2), [Ru (η⁶-p-cymene)Cl (L₃)] (3), respectively. The chloride atom of 2 and 3 was substituted by ambidentate ligands N₃, NCO and NCS to generate a series of ruthenium compounds 4a-4c and 5a-5b. All of these ligands and ruthenium compounds were characterized by ¹H and ¹³C NMR spectroscopy. Compounds 1–3, 4a-4c, and 5a were also structural determined by single crystal X-ray crystallography showing a three-legged piano stool geometry with the p-cymene acting as the seat plane. Anti-proliferative activity study using these ruthenium complexes against PC-3 and DU-145 cell-lines shows that compounds 2 and 4a-4c have the best activity than other ruthenium compounds. The results indicate that the ruthenium p-cymene compounds with large steric hindrance of dehydroacetic acid imine derivative ligands exhibit higher anti-proliferative activity against PC-3 and DU-145 cell-lines.