New polydentate Ru(III)-Salan complexes: Synthesis, characterization, anti-tumour activity and interaction with human serum proteins

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• 作者：Cristina P. Matos^a ; Andreia Valente^a ; Fernanda Marques^b ; Pedro Adã ; o^c ; M. Paula Robalo^c ; ^d ; Rodrigo F.M. de Almeida^e ; Joã ; o Costa Pessoa^c ; Isabel Santos^b ; M. Helena Garcia^a ; Ana Isabel Tomaz^a ; ^{isabel.tomaz@fc.ul.pt}
• 关键词：Ruthenium(III) ; Bis(aminophenolate) ligands ; Salan ligands ; Anti-tumour activity ; Human serum albumin binding
• 刊名：Inorganica Chimica Acta
• 出版年：2013
• 出版时间：1 January, 2013
• 年：2013
• 卷：394
• 期：Complete
• 页码：616-626
• 全文大小：948 K

文摘

Two new Ru(III) complexes bearing tetradentate N₂O₂ bis(aminophenolate) ligands (i.e. Salan-type ligands), were synthesized and characterized. The paramagnetism of the new [Ru^III(Salan)Cl(PPh₃)] (Salan = 4-methoxy/5-methoxy derivatives of 1,4-bis(salycilidene)cyclohexanediamine, PPh₃ = triphenylphosphane) was proved by spectroscopic studies. These complexes exhibit a 4d⁵ low-spin distorted octahedral geometry. The anti-tumour activity of ligands and complexes was screened in vitro against A2780, MCF7 and MDAMB231 human cancer cell lines. Both ligands and complexes exhibit moderate to high cytotoxicity against all investigated cell lines, in some cases surpassing that of Cisplatin. Coordination to the Ru(III) center enhanced the cytotoxicity of each bis(aminophenolate) ligand by at least twofold.

Binding of both Ru(III)-Salan complexes to human serum albumin is strong, as evaluated by steady-state and time-resolved fluorescence spectroscopy, suggesting that this protein might be a transport vehicle in the blood serum for these agents. The cytotoxicity of the protein-bound Ru(III)-Salan complex was assessed, as well as the effect of serum albumin binding on the activity of these complexes.

These new Ru(III)-Salan are the first compounds of this class studied for anti-tumour proposes reported in the literature.