Synthesis of substituted terpyridine nickel nitrate complexes and their inhibitory selectivity against cancer cell lines

• Published in: Journal of inorganic biochemistry 2024-07, Vol.256, p.112554, Article 112554
• Main Authors: Huang, Xin, Wang, Benwei, Sun, Dameng, Chen, Min, Xue, Xingyong, Liu, Hongming, Zhou, Yanling, Ma, Zhen
• Format: Article
• Language: English
• Subjects: Anticancer activity; Molecular docking; Nickel nitrate; Terpyridine
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112554

Six terpyridine‑nickel complexes 1–6 were formed by the coordination of 4′-(4-R-phenyl)-2,2′:6′,2″-terpyridine (R = hydroxyl (L1), methoxyl (L2), methylsulfonyl (L3), fluoro (L4), bromo (L5), iodo (L6)) derivatives to nickel nitrate. The compositions and structures of these complexes were analyzed by Fourier Transform infrared spectroscopy (FT-IR), elemental analyses, electrospray ionization mass spectra (ESI-MS), solid-state ultraviolet-visible (UV–Vis) spectroscopy, and single crystal X-ray diffraction (1, 2 and 4) studies. In vitro anticancer cell proliferation experiments against SiHa (human cervical squamous cancer cell line) cells, Bel-7402 (human hepatoma cancer cell line), Eca-109 (human esophageal cancer cell line) and HL-7702 (human normal hepatocyte cell line) indicate that they have more excellent anti-proliferation effects than the cis-platin against Siha cells, Bel-7402 cells and Eca-109 cells. Especially, complex 5 showed a rather outstanding inhibitory effect against the SiHa cell line and was less toxic than the other compounds to the HL-7702 cell line, implying an obvious specific inhibitory effect. Therefore, complex 5 has the potential value to be developed as an anticancer cell-specific drug against human cervical squamous carcinoma. Molecular docking simulation, UV–vis absorption spectroscopy and circular dichroism experiments show that they prefer to bind to DNA part in an embedded binding manner. Six Ni(II)-terpyridine complexes were fabricated and investigated with excellent anti-proliferative activity than commercial cisplatin, and their interaction with DNA has been experimental and computational studied. These complexes interact with the DNA through an embedded binding mode, thereby hindering the proliferation of cancer cells. [Display omitted] •In vitro cytotoxicity assay indicates that these complexes have higher antiproliferative activities than cisplatin against cancer cells.•One of them exhibited much higher antiproliferation to cancer SiHa cells than cisplatin while low toxicity to normal HL-7702 cells.•Spectroscopic characterization and computational simulation suggest that they tend to exert influence on cells by binding with DNA.