NDLI: Four Cu(II) complexes based on antitumor chelators: synthesis, structure, DNA binding/damage, HSA interaction and enhanced cytotoxicity

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bao, Wei-guo Xie, Cheng-zhi Xu, Jing-yuan Liu, Ya-hong Shao, Jia Song, Xue-qing Li, Ang
Description	Author Affiliation: Liu YH ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Li A ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Shao J ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Xie CZ ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Song XQ ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Bao WG ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.); Xu JY ( Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, P. R. China. xujingyuan@tmu.edu.cn.)
Abstract	Four novel copper(II) complexes $[Cu^{II}(Bp4mT)(μ-Cl)]_{2}$ (1), $[Cu^{II}(μ-Bp4mT)Br]_{2}$ (2), $[Cu^{II}(HBpT)Cl]$ (3), and $[Cu^{II}(HBpT)Br]$ (4) (Bp4mT = 2-benzoylpyridine-4-methylthiosemicarbazone, HBpT = 2-benzoylpyridine thiosemicarbazone), were synthesized and characterized using single-crystal X-ray diffraction, elemental analysis, infrared, and ultraviolet-visible spectroscopy. X-ray analysis revealed that complexes 1 and 2 based on the Bp4mT ligand presented dimeric structures in which the Cu(II) ions were located in a five-coordinated distorted square-pyramidal geometry, whereas both 3 and 4 complexes were mononuclear with the Cu(II) ions exhibiting a tetracoordinated square planar configuration. Their interactions with calf thymus DNA (CT-DNA) were investigated using viscosity measurements and fluorescence spectroscopy. Multispectroscopic evidence has shown interactions between these complexes and human serum albumin (HSA). All these complexes have exhibited efficient oxidative cleavage of supercoiled DNA in the presence of hydrogen peroxide, presumably via an oxidative mechanism. Furthermore, in vitro cytotoxicity studies of 1–4 against human liver hepatocellular carcinoma cells (HepG-2), human large cell lung carcinoma cells (NCI-H460), and human cervical carcinoma cells (HeLa) indicated their promising antitumor activity with quite low $IC_{50}$ values in the range of 0.08–1.98 μM, which are 83 times lower than those of cisplatin. The mechanistic studies revealed that four complexes, which induced early apoptosis, were involved in reactive oxygen species generation and DNA cleavage for their antitumor activities.
ISSN	14779226
Issue Number	19
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-05-10
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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