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

作　　者：Jin-An Zhao Huai-Bin Yu Shuang-Cheng Zhi Rui-Na Mao Ji-Yong Hu Xiao-Xiao Wang 

机构地区：[1]College of Material and Chemical Engineering, Henan University of Urban Construction [2]College of Chemistry and Molecular Engineering, Zhengzhou University

出　　处：《Chinese Chemical Letters》2017年第7期1539-1546,共8页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China (Nos. 21371046, 21401041)

摘　　要：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, 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.

关 键 词：Cu（II）/Co（II） complexes Benzimidazole-based ligand Chemical nuclease activity Apoptosis Anti-cancer agents 

分 类 号：O641.4[理学—物理化学] TQ460.1[理学—化学]