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|Title:||Transition metal complexes with 1-adamantoyl hydrazones - Cytotoxic copper(II) complexes of tri- and tetradentate pyridine chelators containing an adamantane ring system|
|Journal:||European Journal of Inorganic Chemistry|
|Abstract:||Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Five pentacoordinate copper(II) complexes with 2-acetylpyridine or di(2-pyridyl) ketone 1-adamantoyl hydrazone ligands (Adpy and Addpy, respectively) of the formulae [CuCl2(Adpy)] (1), [Cu2(μ-Cl)2(Adpy-H)2] (2), [Cu(NCS)2(Adpy)] (3), [Cu2(μ-Cl)2(Addpy-H)2] (4), and [Cu2(NCS)2(μ-Addpy-H)2] (5) were synthesized and characterized by spectral, electrochemical, and X-ray structural analysis. Flow cytometry and morphological analysis confirmed that the copper(II) complexes 2 and 5 induced accumulation of a sub-G1 phase population, and fluorescence microscopy indicated the presence of large cells in apoptosis. The interaction of the copper(II) complexes with calf thymus DNA (CT-DNA) was monitored by changes in their UV/Vis spectra. The observed intrinsic binding constants for 2 and 5 (Kb = 1.77-×-106 and 3.58-×-106 M-1, respectively) together with ethidium displacement fluorescence experiments indicate intercalative binding. Complexes 2 and 5 showed nuclease activity against pUC19 plasmid DNA. Five CuII complexes with 2-acetylpyridine or di(2-pyridyl) ketone 1-adamantoyl hydrazones have been prepared and physicochemically characterized. All of the tested complexes exhibit strong cytotoxic activity and induce apoptosis as the primary method of cell death. An intercalative mode of interaction with DNA was determined, and pronounced double-strand cleavage of supercoiled DNA was observed.|
|Appears in Collections:||Faculty of Science, Kragujevac|
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