1,3-双苯并咪唑银配合物的合成、抗肿瘤活性及与DNA的相互作用研究  

Synthesis,antitumor activity and interaction with DNA of 1,3-bis-benzimidazole-phenyl-based silver( Ⅰ) complex

作　　者：杨艳芳[1] 林娟娟 李雪华[1] 蒙法艳[1] YANG Yan-fang;LIN Juan-juan;LI Xue-hua;MENG Fa-yan(College of pharmaceutical Sciences,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《化学研究与应用》2018年第7期1106-1113,共8页Chemical Research and Application

基　　金：广西自然科学青年基金项目(2014GXNSFBA20024)资助

摘　　要：以1,3-双苯并咪唑苯和硝酸银为原料,在氨水环境下,140℃反应80 h制备1,3-双苯并咪唑银配合物,用FT-IR和X-射线单晶衍射对1,3-双苯并咪唑银配合物进行表征。通过MTT实验法、流式细胞术及与DNA的相互作用实验,检测1,3-双苯并咪唑银配合物的抗肿瘤活性。X-射线单晶衍射结果表明1,3-双苯并咪唑银配合物属于正交晶系,空间群为Pbcn,晶胞参数a=21.830 9(10),b=13.704 6(7),c=12.576 9(6),V=3 762.8(3)~3,Z=8,μ(Mo Kα)=1.817,F(000)=2032.0,Dc=1.850 g·cm3,最终残差因子R=0.059 2,wR=0.126 7。体外抗肿瘤活性实验MTT检测表明1,3-双苯并咪唑银配合物对肝癌细胞Hep-G2,人宫颈癌细胞Hela和乳腺癌细胞MCF-7均有抑制作用;流式细胞术结果表明1,3-双苯并咪唑银配合物可以诱导Hep-G2细胞凋亡,并在Hep-G2细胞G2期引起细胞周期阻滞;与DNA相互作用实验结果进一步说明1,3-双苯并咪唑银配合物以经典非插入方式与DNA发生相互作用,从而导致DNA损伤并具有抗癌作用。1,3-Bis-benzimidazole-phenyl-based silver（ Ⅰ） complex was synthesized with reactants of 1,3-bisbenzimidazole-phenyl and Ag NO3 at 140 ℃ for 80 h in an ammonia aqueous solution.The structure characterization of 1,3-bis-benzimidazole-phenyl-based silver（ Ⅰ） complex was determined by IR spectroscopy and single crystal X-ray diffraction analysis.The anti-tumor activities of 1,3-Bis-benzimidazole-phenyl-based silver（ Ⅰ） was determined by MTT assay,flow cell apoptosis and DNA binding studies.X-ray analysis showed that 1,3-bis-benzimidazole-phenyl-based silver（ Ⅰ） complex belongs to a orthorhombic system,the space group was Pbcn with a = 21. 830 9（ 10） ,b = 13. 704 6（ 7） ,c = 12. 576 9（ 6） ,V = 3 762. 8（ 3） ~3,Z = 8,μ（ Mo Kα） = 1. 817,F（ 000） = 2032. 0,Dc = 1. 850 g·cm^-3 and the final R = 0. 059 2,wR = 0. 126 7. 1,3-Bis-benzimidazole-phenyl-based silver（ Ⅰ） complex exhibited cytotoxicity against hepatocellular carcinoma（ Hep-G2）,human cervical（ Hela） and breast adenocarcinoma（ MCF-7） cells,while free ligands were cytotoxically inactive during in vitro anticancer activities by MTT test.Flow cytometric analysis indicateed that 1,3-bis-benzimidazole-phenyl-based silver（ Ⅰ） complex could induce Hep-G2 cell apoptosis,and further studies revealed that 1,3-bisbenzimidazole-phenyl-based silver（ Ⅰ） complex caused cell cycle arrest at G2 phase in Hep-G2 cells. The results of DNA binding studies indicated that 1,3-bis-benzimidazole-phenyl-based silver（ Ⅰ） complex could bind to DNA by partial intercalation,which will consequently lead to DNA damage and had an anticancer effect.

关 键 词：苯并咪唑 银配合物 X-射线单晶衍射 抗肿瘤活性 

分 类 号：O626[理学—有机化学]