Synthesis, crystal structures and anticancer studies of Ni (Ⅱ) and Co (III) complexes based on 2-(2-aminophenyl)-1H-benzimidazole Schiff base derivatives

Two new ligands, 2-(5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazolin-6-yl)phenol (H 2 L1′) and 2-(5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazolin-6-yl)-4-fluorophenol (H 2 L2′) were synthesized by 2-(2-aminophenyl)benzimidazole with salicylaldehyde and 5-fluorosalicylaldehyde, respectively. While the two ligands (H 2 L1′ and H 2 L2′) were coordinated with nickel (II) and cobalt (II) ions and represented open-chain Schiff base structures (H 2 L1 and H 2 L2). Their metal complexes: [Ni 2 (HL1) 2 (C 2 H 5 OH) 2 Cl 2 ]‧2C 2 H 5 OH (complex 1), [Co (HL1) (L1)] (complex 2), [Ni 2 (HL2) 2 (C 2 H 5 OH) 2 Cl 2 ]‧2C 2 H 5 OH (complex 3) and [Co (HL2) (L2)] (complex 4) were obtained by solvothermal reaction. The four Schiff base complexes were characterized by infrared spectroscopy, elemental analysis, thermal stability analysis, X-ray powder diffraction, single-crystal X-ray diffraction, and lipophilicity assay. Single crystal X-ray analysis reveals that complexes 1 and 3 crystallize in a monoclinic system with space group P 21/n, while complexes 2 and 4 crystallize in a trigonal system with space group R -3. The lipophilicity assay (Log P) showed that the introduction of fluorine atoms enhanced the lipophilicity of ligands and complexes. The MTT method was used to determine the IC 50 values of complexes, ligands, and cisplatin against four different tumor cells (A-549, SMMC-7721, MDA-MB-231, and CNE-2Z) and one normal cell (IOSE 80). The results indicated that the four complexes exhibited stronger anticancer efficacy than ligands, among which the fluorine-substituted Co (III) complex (complex 4) displayed greater cytotoxicity compared with cisplatin in inhibiting SMMC-7721, MDA-MB-231 cells and A-549 cells, respectively. In addition, complex 4 can increase intracellular reactive oxygen species levels, arrest cells in the G0/G1 phase, upregulate Bax levels, and downregulate Bcl-2 levels, inducing MDA-MB-231 cell apoptosis in a dose-dependent manner.