Synthesis, cytotoxicity and anti-metastatic properties of new pyridyl-thiazole arene ruthenium(II) complexes

A series of novel ruthenium(II)-cymene complexes (1-8) containing substituted pyridyl-thiazole ligands, [Ru(eta(6)-p-cymene)(L)Cl]Cl (L = N,N-chelating derivatives), have been synthesized and characterized using elemental analysis, infrared, H-1 NMR and C-13 NMR spectroscopies and mass spectrometry. All these complexes not only display marked cytotoxicity in vitro against three different human cancer cell lines (HeLa, A549 and MDA-MB-231), but also exhibit promising anti-metastatic activity at sub-cytotoxic concentrations. Cell cycle analysis shows that the ruthenium(II) complex-induced growth inhibition was mainly caused by S-phase cell cycle arrest. Further protein level analysis suggests that compound 5 may exert antitumor activity via a p53-independent mechanism.