期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 105, 期 5, 页码 728-737出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2011.01.004
关键词
Copper(II) complex; Schiff base ligand; DNA cleavage activity; Apoptosis; Anticancer activity
资金
- National Natural Science Foundation of China [20971099]
- Tianjin Medical University [2010GS105]
A new cytotoxic copper(II) complex with Schiff base ligand [Cu-II(5-Cl-pap)(OAc)(H2O)]center dot 2H(2)O (1) (5-Cl-pap = N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine), was synthesized and structurally characterized by X-ray diffraction. Single-crystal analysis revealed that the copper atom shows a 4+1 pyramidal coordination, a water oxygen appears in the apical position, and three of the basal positions are occupied by the NNO tridentate ligand and the fourth by an acetate oxygen. The interaction of Schiff base copper(II) complex 1 with DNA was investigated by UV visible spectra, fluorescence spectra and agarose gel electrophoresis. The apparent binding constant (K-app) value of 6.40 x 10(5) M-1 for 1 with DNA suggests moderate intercalative binding mode. This copper(II) complex displayed efficient oxidative cleavage of supercoiled DNA, which might indicate that the underlying mechanism involve hydroxyl radical, singlet oxygen-like species, and hydrogen peroxide as reactive oxygen species. In addition, our present work showed the antitumor effect of 1 on cell cycle and apoptosis. Flow cytometric analysis revealed that HeLa cells were arrested in the S phase after treatment with 1. Fluorescence microscopic observation indicated that complex 1 can induce apoptosis of HeLa cells, whose process was mediated by intrinsic mitochondrial apoptotic pathway owing to the activation of caspase-9 and caspase-3. (C) 2011 Elsevier Inc. All rights reserved.
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