期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 117, 期 -, 页码 171-188出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2012.07.022
关键词
Ruthenium(II) arene complexes; Aminophosphines; Anticancer drugs; Cytotoxicity; Metal-based drugs; DNA interaction
资金
- MINECO of Spain [CTQ-2011-24434]
Aminophosphines 2-(diphenylphosphino)-1-methylimidazole (dpim) and diphenyl-2-pyridylphosphine (PPh(2)py) have been used to prepare two series of Ru(II) arene complexes of formulae [(eta(6)-p-cymene) Ru(kappa(2)-O,O'-X)(kappa(1)-P-dpim)]Y (series a: 1a.Y-3a.Y) and [(eta(6)-p-cymene)Ru(kappa(2)-O,O'-X)(kappa(1)-P-PPh(2)py)]Y (series b: 1b.Y-3b.Y) (where X=acac, acetylacetonate; bzac, benzoyl acetonate; dbzm, dibenzoyl methanoate; Y=BF4, BPh4). The structures of 1a.BF4, 1a.BPh4, 3a.BF4, 1b.BPh4 and 3b.BPh4 were determined by X-ray diffraction. The tetrafluoroborate derivatives are more soluble in organic solvents than their tetraphenylborate counterparts. Five BF4- derivatives (all except the unstable 1b.BF4) were selected to evaluate the cytotoxic behavior in vitro against the human cancer cell lines MCF-7 (breast cancer) and CAPAN-1 (pancreatic cancer). 2b.BF4 and 3b.BF4 exhibited IC50 values similar to those of cisplatin. Electrophoresis and AFM studies showed good correspondence between the biological activity levels of 2b.BF4 and 3b.BF4 and their ability to modify the DNA structure. Hydrolytic studies indicate that aquation could be involved in the activation mechanism of these complexes and confirm that the hydrolysis rate of 3b.BF4 is higher than that of 3a.BF4. Thus, the cytotoxic activity trends are explained in terms of the higher reactivity of derivatives from series b, which in turn is rationalized as being the result of the electronic features of dpim and PPh(2)py established by cyclic voltammetry measurements. (C) 2012 Elsevier Inc. All rights reserved.
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