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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Synthesis, Characterization, DNA/HSA Interactions, and Anticancer Activity of Two Novel Copper(II) Complexes with
Zhen-Fang Zeng1, Qiu-Ping Huang1, Jie-Hui Cai1
1School of Chemical and Biological Engineering, Guangxi Normal University for Nationalities, 23 Fozi Road, Chongzuo 532200, China.
Abstract:
The purpose of this study was to identify new metal-based anticancer drugs; to this end, we synthesized two new copper(II) complexes, namely [Cu(ncba)4(phen)] (1) and [Cu(ncba)4(bpy)] (2), comprised 4-chloro-3-nitrobenzoic acid as the main ligand. The single-crystal XRD approach was employed to determine the copper(II) complex structures. Binding between these complexes and calf thymus DNA (CT-DNA) and human serum albumin (HSA) was explored by electronic absorption, fluorescence spectroscopy, and viscometry. Both complexes intercalatively bound CT-DNA and statically and spontaneously quenched DNA/HSA fluorescence. A CCK-8 assay revealed that complex 1 and complex 2 had substantial antiproliferative influences against human cancer cell lines. Moreover, complex 1 had greater antitumor efficacy than the positive control cisplatin. Flow cytometry assessment of the cell cycle demonstrated that these complexes arrested the HepG2 cell cycle and caused the accumulation of G0/G1-phase cells. The mechanism of cell death was elucidated by flow cytometry-based apoptosis assays. Western blotting revealed that both copper(II) complexes induced apoptosis by regulating the expression of the Bcl-2(Bcl-2, B cell lymphoma 2) protein family.
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