Potential anticancer activity of benzimidazole-based mono/dinuclear Zn(II) complexes towards human carcinoma cells

• Published in: Polyhedron Vol. 102; pp. 163 - 172
• Main Authors: Zhao, Jin’an, Guo, Yan, Hu, Jiyong, Yu, Huaibin, Zhi, Shuangcheng, Zhang, Junshuai
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 14.12.2015
• Subjects: Apoptosis; Cytotoxic activity; DNA binding; SHSY5Y cells; Zn(II) complexes; Zn(II) complexes; SHSY5Y cells; DNA binding; Cytotoxic activity; Apoptosis
• ISSN: 0277-5387
• DOI: 10.1016/j.poly.2015.09.057

To investigate the biological activities of Zn(II) complexes, two mono/dinuclear Zn(II) complexes, Zn2(p-2-bmb)2 (NO3)2 (1) and Zn(p-2-bmp)2Cl2 (2), were constructed from V-shape flexible benzimidazole-based ligands. Compared with complex 2, in cytotoxicity research, 1 showed higher cytotoxic properties in vitro against SHSY5Y cells. The interaction of complex 1 with calf thymus DNA is not the classical intercalation binding. Flow cytometry analyses demonstrated that complex 1 arrested the cells in the G0/G1 phase with a dose-dependent manner. In addition, the morphological changes and membrane permeability changes also provide evidence that 1 could induce apoptosis. [Display omitted] Two Zn(II) complexes bearing benzimidazole-based derivatives, namely Zn2(p-2-bmb)2 (NO3)4 (1) and Zn(p-2-bmp)2Cl2 (2) (p-2-bmb=1-((2-(pyridin-2-yl)-1-benzoimidazol-1-yl)methyl)-1H-benzotriazole, p-2-bmp=1-((2-(pyridine-2-yl)-1H-benzoimidazol-1-yl)methyl)-1H-pyridine) were constructed and their biological activities against four human cancer cell lines were estimated. Compared with complex 2, in cytotoxicity research complex 1 showed higher cytotoxic properties in vitro against different carcinoma cells, especially for SHSY5Y cells. The interactions of complex 1 with calf thymus DNA were studied by spectroscopic techniques, including absorption and fluorescence, which showed the binding mode of 1 is not the classical intercalation binding. The optimum antiproliferative activity of complex 1 in SHSY5Y cells was found to involve G0/G1 phase arrest of the cell cycle. In addition, the morphological changes and membrane permeability changes also provide evidence that 1 could induce apoptosis.