Complexes [Ru(η6 -C10 H14 )(Cl2 )(HdmoPTA)](OSO2 CF3 ) (1), [Ru(η6 -C10 H14 )(Cl2 )(dmoPTA)] (2) and [Ru(η6 -C10 H14 )(Cl2 )-μ-dmoPTA-1κP:2κ2 N,N'-MCl2 ] (M=Zn (3), Co (4), Ni (5), dmoPTA=3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) have been synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structures of 1, 3 and 5 were obtained by single-crystal X-ray diffraction. The antiproliferative activity of the complexes was evaluated against colon cancer cell line Caco-2/TC7 by using the MTT protocol. The monometallic ruthenium complexes 1 and 2 were found to be inactive, but the bimetallic complexes 3, 4 and 5 display an increased activity (IC50 3: 9.07±0.27, 4: 5.40±0.19, 5: 7.15±0.30 μM) compared to cisplatin (IC50 =45.6±8.08 μM). Importantly, no reduction in normal cell viability was observed in the presence of the complexes. Experiments targeted to obtain information on the possible action mechanism of the complexes, such as cell cycle, ROS and gene expression studies, were performed. The results showed that the complexes display different properties and action mechanism depending on the nature of metal, M, bonded to the CH3 NdmoPTA atoms.
Keywords: antiproliferative activity; apoptosis; bis-heterometallic complexes; caspases; cell cycle; ruthenium.
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