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Nickel chloride complexes with substituted 4′-phenyl-2′,2′:6′,2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions

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Abstract

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4′-(4-substituent phenyl)-2′,2′:6′,2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI–MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223 μM and 0.335 μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

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Funding

This study was funded by National Natural Science Foundation of China (Nos. 21261002, 31660251, 31860245, 31960203).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, Guangxi, People’s Republic of China

    Benwei Wang, Dameng Sun, Sihan Wang, Min Chen, Hongming Liu, Yanling Zhou & Zhen Ma

  2. School of Animal Science and Technology, Guangxi University, Nanning, 530004, Guangxi, People’s Republic of China

    Hailan Chen

  3. Guangxi Key Laboratory of Marine Natural Products and Combinatorial Biosynthesis Chemistry, Guangxi Beibu Gulf Marine Research Center, Guangxi Academy of Sciences, Nanning, 530007, Guangxi, People’s Republic of China

    Hailan Chen

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  1. Benwei Wang
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Wang, B., Sun, D., Wang, S. et al. Nickel chloride complexes with substituted 4′-phenyl-2′,2′:6′,2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions. J Biol Inorg Chem 28, 627–641 (2023). https://doi.org/10.1007/s00775-023-02011-3

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