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

Abstract

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.