Ruthenium (II) complexes containing dehydroacetic acid and its imine derivative ligands. Synthesis, characterization and cancer cell growth anti-proliferation activity (GI 50 ) study

Abstract Two dehydroacetic acid (DHA, L 1 H ) related imine ligands, L 2 H and L 3 H were obtained in moderate yields by reacting DHA with 2,4,6-trimethylaniline and phenylhydrazine, respectively. Refluxing [Ru (η 6 - p -cymene)Cl 2 ] 2 with two equivalents of L 1 Na , L 2 H and L 3 H in methanol generated ruthenium compounds [Ru (η 6 - p -cymene)Cl (L 1 )] ( 1 ), [Ru (η 6 - p -cymene)Cl (L 2 )] ( 2 ), [Ru (η 6 - p -cymene)Cl (L 3 )] ( 3 ), respectively. The chloride atom of 2 and 3 was substituted by ambidentate ligands N 3 , 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 1 H and 13 C 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.