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DNA cleavage, DNA/HSA binding study, and antiproliferative activity of a phenolate-bridged binuclear copper(II) complex

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Abstract

A novel phenolate-bridged binuclear copper(II) complex, [Cu II2 (L–3H)Cl] (1, where L = 2,6-bis[((2-hydroxybenzyl)(2-pyridylmethyl)amino)methyl]-4-methylphenol), have been synthesized and characterized. The antiproliferative activity of the complex has been tested in vitro against the human cervical cancer cell line HeLa, human non-small-cell lung cancer cell line A-549, the human breast cancer cell line MCF-7, and the human hepatic cell line LO2. The results show the complex has the low micromolar range (9.4–11.2 µM) of IC50 values towards the three cancer cell lines, which is markedly comparable to those of cisplatin. However 1 exhibited 10.6-fold less toxicity than cisplatin toward normal cells LO2, suggesting that complex 1 had high selectivity between tumor cells and normal cells. The interactions with DNA were investigated by UV–Vis absorption, fluorescence, circular dichroism, and gel electrophoresis. The results show that the copper(II) complex could strongly bind to DNA mainly by the groove binding mode and efficiently cleave the pBR322 plasmid DNA into its nicked and linear forms in the presence of excessive ascorbic acid. In addition, the evaluation of the protein binding ability shows that complex 1 could bind to human serum albumin (HSA) with a moderate binding affinity and quench the intrinsic fluorescence of HSA.

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Acknowledgements

We acknowledge the financial support from the Natural Science Foundation of Hubei Province (No. 2018CFB658) and the Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices, Ministry of Education, Jianghan University (No. JDGD-201810).

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  1. Flexible Display Materials & Technology, Co-Innovation Center of Hubei, Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Chemistry and Environmental Engineering, Jianghan University, Wuhan, 430056, People’s Republic of China

    Zhanfen Chen, Yixuan Wu & Yumin Zhang

  2. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210017, People’s Republic of China

    Zhenzhu Zhu

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  1. Zhanfen Chen
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Chen, Z., Wu, Y., Zhu, Z. et al. DNA cleavage, DNA/HSA binding study, and antiproliferative activity of a phenolate-bridged binuclear copper(II) complex. Biometals 32, 227–240 (2019). https://doi.org/10.1007/s10534-019-00172-w

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