Synthesis, Structures and Antiproliferative Activity of Novel Ru(II)-Arene Complexes with N,O-Chelating β-Ketoamine Ligands

Organometallic compounds are attracting a considerable interest in medicinal chemistry, especially as putative anticancer compounds. Of particular interest are ruthenium-arene complexes which have been extensively studied and modified to obtain compounds with various therapeutic effects. Ruthenium arene complexes with β-ketoamine ligands derived from 4-acyl-5-pyrazolones possess relevant anticancer properties in vitro. It was found that minor changes to the β-ketoamine ligand lead to considerable changes in cytotoxicity and, consequently, a series of novel Ru(II)-arene derivatives containing β-ketoamine ligands L' (HL' in general, HLbiph,ph, HLbiph,naph, HLph,naph, HLhex,naph) has been synthetized and fully characterized by spectroscopy and single-crystal X-ray diffraction. The ligands in the anionic form coordinate to the ruthenium ion in a chelating κ2 N,O-bidentate mode, affording 1:1 derivatives of the formula [(arene)Ru(L')Cl]. The in vitro anticancer activity of both the ligands and complexes has been evaluated against the human ovarian carcinoma cell line A2780 and its cisplatin-resistant equivalent A2780R.