Publication Type Thesis
Title Synthesis of new 3D-?5-carboranyl and ?5-methylcyclopentadienyl ruthenium complexes incorporating bipyridine (macro)ligands as promising anticancer agents
Authors Ricardo G. Teixeira
Groups BIOIN
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Year 2017
Month July
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Abstract Cancer is considered one of the leading causes of death worldwide. Therefore, the search for potential anticancer drugs is nowadays a mandatory topic and many research groups focus their interests and efforts in this area. About 50-70 % of all tumors are treated with platinum based compounds (cisplatin, carboplatin and oxaliplatin) but due to several and severe side effects caused by these metallodrugs and to the resistance phenomena (acquired or intrinsic), complexes with metal ions other than platinum, have been widely investigated for their anticancer properties. In this frame, ruthenium appears as a strong candidate for drug development showing low toxicity, selectivity for tumors, inhibition of metastasis progression and antiangiogenic properties. Within this project, seven new organometallic compounds were synthesized and characterized. The successful formulation of these complexes, with general formula [Ru(?5-MeCp)(PPh3)(4,4’-R2-2,2’-bipy)]][CF3SO3] (1a, R = -CH3; 1b, R = -CH2OH; 1c, R = -O(CH2)3(CF2)7CF3; 1d, R = -CH2OPLA) or [3-CO-3,3-{k2-4,4’-R2-2,2’-bipy}-closo-3,1,2-RuC2B9H11] (2a, R = -CH3; 2b, R = -CH2OH; 2c, R = -CH2OPLA) was supported by spectroscopic (NMR, UV-Vis, FTIR), electrochemical (cyclic voltammetry) and structural (single crystal X-ray diffraction) data. When applicable, the purity was evaluated through elemental analysis. The stability of all compounds was tested by electronic spectroscopy using DMSO/DMEM as solvents, over a period of 24 hours. All complexes displayed an adequate stability (average of less than 6 % variation over a 24 hours period) which proved to be adequate to proceed to the in vitro biological screening assays. The partition coefficient in n-octanol/water, Pow, was also determined when the solubility of the compounds allowed it, showing that, generally, these compounds are lipophilic. The cytotoxicity of the complexes was evaluated in vitro in a panel of human cancer cell lines namely A2780 (human ovary adenocarcinoma), A375 (human melanoma), and RKO and SW480 (human colon adenocarcinoma), within a 24 h or 48 h incubation time. The results obtained for all the cell lines tested confirm the potential of these two families of compounds as anticancer agents in traditional chemotherapy (compounds 1a-1d) or in Boron Neutron Capture Therapy (BNCT, compounds 2a-2c). Keywords Ruthenium(II) complexes ?5-Methylcylopentadienyl 3D-?5-Carboranyl Polymer-metal conjugates Anticancer agents
DOI http://dx.doi.org/
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Observations URI: http://hdl.handle.net/10451/31808
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