Synthesis, structure, and anticancer activity of Ni(II) complexes derived from polyhalogenated 2-aminophenol Schiff bases.

Six Schiff bases (H₂L1-H₂L6) were synthesized by the reaction of 3,5-substituted salicylaldehyde (F/Cl/Br) with 2-amino-4-substituted phenol (F/Cl/Br), and their Ni(II) complexes (C1-C6) were obtained with NiCl₂·6H₂O, respectively. All complexes were characterized via infrared spectroscopy, NMR spectra analysis, UV-visible spectroscopy, thermal stability analysis, elemental analysis, X-ray powder diffraction, single-crystal X-ray diffraction, ICP-OES analysis, and lipophilicity assay. Single crystal X-ray analysis reveals that complexes C1, C4, C5, and C6 crystallize in a monoclinic system with space group I4/a, while complexes C2 and C3 crystallize in the trigonal system with space group P-1. The cytotoxicity of polyhalogenated 2-amino-phenol Schiff base ligands and their metal complexes on breast cancer cells (SKBR3), nasopharyngeal carcinoma cells (CNE-2Z), lung cancer cells (A549), rectal cancer cells (HCT-116) and two types of normal human cells (IOSE 80 and MCF-10 A) was determined by MTT assay. The results showed that C1-C6 complexes exhibited stronger anticancer efficacy on SKBR3 cells than ligands and cisplatin. Among them, C5, C6 and C4 could increase intracellular reactive oxygen species levels, reduce the mitochondrial membrane potential, arrest cells in the G0/G1 phase, induce SKBR3 cell apoptosis in a dose-dependent manner and promote Bax protein expression and inhibit Bcl-2 protein expression in vitro experiments. In vivo experiments showed that the C5 complex significantly suppressed SKBR3 tumor growth with low toxicity to major organs in the nude mice model.