The Significant Influence of a Second Metal on the Antiproliferative Properties of the Complex [Ru(η6?C10H14)(Cl2)(dmoPTA)] |
| |
Authors: | Dr Nazanin Kordestani Dr Elisa Abas Dr Laura Grasa Andres Alguacil Dr Franco Scalambra Prof Antonio Romerosa |
| |
Institution: | 1. Área de Química Inorgánica-CIESOL Facultad de Ciencias, Universidad de Almería, Carr. Sacramento, s/n, 04120 La Cañada, Almería, Spain;2. Departamento de Farmacología, Fisiología y Medicina Legal y Forense Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet, 177, 50013 Zaragoza, Spain;3. Departamento de Farmacología, Fisiología y Medicina Legal y Forense Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet, 177, 50013 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS Aragón), San Juan Bosco, 13, 50009 Zaragoza, Spain
Instituto Agroalimentario de Aragón -IA2-, Universidad de Zaragoza–CITA), Miguel Servet, 177, 50013 Zaragoza, Spain |
| |
Abstract: | Complexes Ru(η6?C10H14)(Cl2)(HdmoPTA)](OSO2CF3) ( 1 ), Ru(η6?C10H14)(Cl2)(dmoPTA)] ( 2 ) and Ru(η6?C10H14)(Cl2)-μ-dmoPTA-1κP:2κ2N,N’-MCl2] (M=Zn ( 3 ), Co ( 4 ), Ni ( 5 ), dmoPTA=3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo3.3.1]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 CH3NdmoPTA atoms. |
| |
Keywords: | antiproliferative activity apoptosis bis-heterometallic complexes caspases cell cycle ruthenium |
|
|