Discovery of organometallic Ruthenium(II)-arene complexes of lidocaine as improved photocytotoxic agents

Abstract

The new family of Ruthenium(II)-arene complexes of lidocaine of formula [RuII(η6-p-cymene)Cl(LC)](PF6), 1, [RuII(η6-p-cymene) (CCFc) (LC)](PF6), 2, [RuII(η6-p-cymene) (CCFcIP) (LC)](PF6), 3 (LC: lidocaine, FcCCH: ferrocenyl acetylene, CCFcIP: 1′-(phenanthro[9,10-d]imidazole) ferrocenyl-1-acetylene) were prepared and characterized by ESI-MS spectrometry, elemental analysis, IR, 1H and 13C NMR spectroscopy. The photocytotoxicity of 1–3 was studied with visible light (400–700nm) against a panel of human cancer cell lines namely, A-375 (human melanoma), HeLa (human cervical cancer) and MCF-7 (human breast cancer) cancer cells. The photoactivity follows the order 1<2<3 with 2 and 3 having IC50 values in A-375 (melanoma) cells in the low micromolar range. These complexes interact with calf thymus DNA. The photocleaving pUC19 DNA of complexes with visible light (400–700nm) was studied and the results exhibited the active involvement of superoxide and hydroxyl radicals as the reactive oxygen species (ROS) in the DNA photocleavage reactions. These complexes interact with calf thymus DNA via intercalative mode that binding constants vary in the order: 3>2>1. The complexes 2 and 3 were photoactivated in A-375 cells by visible radiation and analyzed by alkaline single-cell gel electrophoresis.