DNA interactions and anticancer screening of copper(II) complexes of N-(methylpyridin-2-yl)-amidino-O-methylurea
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Cu(II) complexes of the tridentate ligand N-(methylpyridin-2-yl)-amidino-O-methylurea (L), namely [Cu(L)Cl2] and [Cu(L)ClO4]ClO4, have been investigated for interactions with DNA by spectroscopic methods and viscosity measurements. Both complexes bind to DNA through non-intercalative interactions. [Cu(L)Cl2] (K b = 2.81 × 105 M−1) shows similar DNA-binding potential to [Cu(L)ClO4]ClO4 (K b = 1.57 × 105 M−1). Investigation of the chemical nuclease properties toward plasmid pBR322 DNA by gel electrophoresis and atomic force microscopy (AFM) suggests that both complexes are able to cleave the supercoiled form (Form I) to the nicked (Form II) and linear forms (Form III) through an oxidative pathway. The possible reactive oxygen species have been investigated by the use of scavengers, indicating that hydroxyl radicals may be involved in the DNA cleavage mechanism. Both of these complexes show similar activities against selected human cancer cell lines.
KeywordsCircular Dichroism Spectrum Ethidium Bromide Nuclease Activity Absorption Titration Intrinsic Binding Constant
This work was financially supported by Center of Excellence for Innovation in Chemistry (PERCH-CIC) and the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Communication, through the Advanced Functional Materials Cluster of Khon Kaen University. P.G. acknowledges ICREA (Institució Catalana de Recerca i Estudis Avançats), the Ministerio de Economía y Competitividad of Spain (Project CTQ2011-27929-C02-01), and the support of COST Actions CM1003 and CM1105.
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