Synthesis, chemical nuclease activity, and in vitro cytotoxicity of benzimidazole-based Cu(Ⅱ)/Co(Ⅱ)

来源 :Chinese Chemical Letters | 被引量 : 0次 | 上传用户:tianyawoaiai
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In this study, novel mono/di-nuclear Cu(p-2-bmb)(OH)(Cl O4)(1) and Co2(p-2-bmb)2Cl4(2)(p-2-bmb = 1-((2-(pyridin-2-yl)-benzoimidazol-1-yl)methyl)-1H-benzotriazole) complexes with the nitrogen heterocyclic benzimidazole-based ligand were synthesized and characterized. The two complexes showed antiproliferative effects in various carcinoma cell lines, especially complex 1 in the SMMC7721 tumor cell line. Complex 1 was also able to pass through the cell membrane and enter the nucleus and mitochondrion. An analysis of in vitro chemical nuclease activity revealed that complex 1 partially intercalated to calf thymus DNA and exhibited strong unwinding activity against p BR322 superhelical plasmid DNA. The comet assay and flow cytometry analysis confirmed that 1 caused extensive DNA damage and arrested SMMC7721 tumor cells at G2/M phase of the cell cycle, leading to loss of mitochondrial membrane potential and apoptosis. These results suggest that these benzimidazole-based metal complexes could be potential anti-cancer agents. In this study, the novel mono / di-nuclear Cu (p-2-bmb) (OH) (ClO4) (1) and Co2 (p-2-bmb) 2Cl4 (2) (2- (pyridin-2-yl) -benzoimidazol-1-yl) methyl) -1H-benzotriazole) complexes with the nitrogen heterocyclic benzimidazole-based ligand were synthesized and characterized. The two complexes showed antiproliferative effects in various carcinoma cell lines , especially complex 1 in the SMMC7721 tumor cell line. Complex 1 was also able to pass through the cell membrane and enter the nucleus and mitochondrion. An analysis of in vitro chemical nuclease activity revealed that complex 1 partially intercalated to calf thymus DNA and said strong unwinding activity against p BR322 superhelical plasmid DNA. The comet assay and flow cytometry analysis confirmed that 1 caused extensive DNA damage and arrested SMMC7721 tumor cells at G2 / M phase of the cell cycle, leading to loss of mitochondrial membrane potential and apoptosis. These results suggest that these benzimidazole-based metal complexes could be potential anti-cancer agents.
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