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化学学报
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化学学报 ›› 2009, Vol. 67 ›› Issue (14): 1573-1578. 上一篇    下一篇

研究论文

四氯合钯(II)喹诺酮配合物的合成及与DNA的作用和抗增殖活性

胡瑞定*,a,b 俞庆森a 易平贵c

  

  1. (a浙江大学化学系 杭州 310027)
    (b浙江师范大学化学与生命科学学院 金华 321004)
    (c湖南科技大学化学化工学院 湘潭 411201)

  • 投稿日期:2008-10-07 修回日期:2009-01-21 发布日期:2009-07-28
  • 通讯作者: 胡瑞定

Synthesis and Interaction with DNA and Antiproliferative Activities of Complexes of Quinolones with Tetrachloropalladium(II)

Hu, Ruiding *,a,b Yu, Qingsen a Yi, Pinggui c

  

  1. (a Department of Chemistry, Zhejiang University, Hangzhou 310027)
    (b College of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004)
    (c School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201)
  • Received:2008-10-07 Revised:2009-01-21 Published:2009-07-28
  • Contact: Hu, Ruiding

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被引次数

16 | 1

在酸性条件下, 分别合成了四氯合钯(II)离子与2种喹诺酮(诺氟沙星, NFLX＝C16H18N3O3F; 环丙沙星, CPLX＝C17H18N3O3F)离子形成的配合物(NFLXH)2[PdCl4]•2H2O (1)和(CPLXH)2[PdCl4]•2H2O (2). 用元素分析、IR、UV以及摩尔电导测定等方法对其进行了表征. 配合物1的晶体结构经X射线单晶衍射确定, 结构参数: 三斜晶系, P-1空间群, a＝0.84561(17) nm, b＝0.94191(19) nm, c＝1.2832(3) nm; α＝111.26(3)°, β＝97.23(3)°, g＝96.38(3)°, V＝0.9312(4) nm3, Z＝1, 最后吻合因子R＝0.040, wR＝0.088. 利用紫外光谱法、荧光光谱法对配合物与小牛胸腺DNA (ct-DNA)的作用进行了研究, 研究表明, 配合物对DNA的作用模式为插入作用, 与DNA的结合常数Kb分别为: Kb(1)＝2.06×104, Kb(2)＝2.43×104. 其后测试了配合物对体外肿瘤细胞的抗增殖活性. 经采用四甲基偶氮唑蓝分析法(MTT法)测试后发现配合物1和2对人肺腺癌A549细胞、人原髓细胞白血病HL-60细胞的增殖抑制作用显著强于相应的喹诺酮分子本身, 其中配合物2对人肺腺癌A549细胞增殖有明显的抑制作用, 抑制率可高达(95.4±3.7)%, 半数抑制浓度(IC50, 72 h)为(124.5±10.3) μmol•L－1.

关键词: 喹诺酮, 诺氟沙星, 环丙沙星, 钯(II), DNA, 抗增殖活性

The complexes of norfloxacin (NFLX＝C16H18FN3O3), ciprofloxacin (CPLX＝C17H18FN3O3) with palladium ion [(NFLXH)2[PdCl4]•2H2O (1), (CPLXH)2[PdCl4]•2H2O (2)] were synthesized under an acidic condition. Complex 1 is orange crystal and complex 2 is brown powder. By means of elemental analysis, IR, UV and molar conductance, the structures of the complexes were characterized. The structure of 1 was determined by single crystal X-ray crystallography, which is of triclinic space group P-1 with a＝0.84561(17) nm, b＝0.94191(19) nm, c＝1.2832(3) nm; α＝111.26(3)°, β＝97.23(3)°, g＝96.38(3)°, V＝0.9312(4) nm3, Z＝1, R＝0.040 and wR＝0.088. The interactions between the complexes and ct-DNA were studied by ultraviolet absorption spectroscopy and fluorescence spectroscopy, indicating that the binding mode is intercalation and the binding constants (Kb) of the complexes with DNA respectively is: 2.06×104 (1), 2.43×104 (2). Antiproliferative activities of the complexes to tumors in vitro were tested by using an 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, showing that the complexes have more powerful inhibition effects on A549 cells and on HL-60 cells growth than quinolone itself. 2 has obvious inhibition effect on A549 cells growth: inhibition ratio on A549 cells reached (95.4±3.7)% and its IC50 (72 h) on A549 cells was (124.5±10.3) μmol•L－1.

Key words: quinolone, norfloxacin, ciprofloxacin, palladium, DNA, antiproliferative activity