具有抗肿瘤活性的6,7-二氰基-二吡啶基[2,2-d:2',3'-f]喹喔啉合钴(II)配合物的合成、晶体结构及与DNA结合的研究

具有抗肿瘤活性的6,7-二氰基-二吡啶基[2,2-d:2',3'-f]喹喔啉合钴(II)配合物的合成、晶体结构及与DNA结合的研究

徐志栋, 刘河, 王敏, 肖苏龙, 杨铭^*, 卜显和

1.北京大学天然药物与仿生药物国家重点实验室, 北京 100083;
2.南开大学化学系, 天津 300071

收稿日期:2002-03-10 修回日期:2002-07-27 出版日期:2002-12-15 发布日期:2002-12-15
通讯作者: 杨铭*

Cobalt (II) Complex of 6,7-Dicycanodipyridoquinoxaline with Antitumor Activities: Synthesis, Crystal Structure and Binding with DNA

Xu Zhidong, Liu He, Wang Min, Xiao Sulong, Yang Ming^*, Bu Xianhe

1. National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083;
2. Department of Chemistry, Nankai University, Tianjin 300071

Received:2002-03-10 Revised:2002-07-27 Online:2002-12-15 Published:2002-12-15
Contact: Yang Ming*

摘要/Abstract

摘要：

合成了6,7 二氰基二吡啶[2,2-d :2',3'-f]喹喔啉(L)与钴(II)形成的配合物[CoL(NO3)2(CH3CN)](1)。通过元素分析、IR对其组成和性质进行了表征, 并测定了它的晶体结构。结果表明, 钴原子与3个N原子和四个O氧原子形成变形五角双锥配位构型。体外抗肿瘤活性筛选试验结果表明:该配合物具有强的抗肿瘤活性, 且配合物活性明显优于配体。通过紫外滴定、粘度滴定、解链温度测定等方法研究了化合物及配体与CT DNA的作用模式及结合常数,结果表明配合物与CT DNA的作用模式为典型的嵌插作用, 配合物和配体与CT DNA的结合常数分别为4.43×10⁵mol·L^-1和1.65×10⁵mol·L^-1。

关键词: Co(II)配合物, 6,7-二氰基二吡啶基[2,2-d:2',3'-f]喹喔啉, 抗肿瘤活性, 晶体结构, DNA结合

Abstract: A novel complex Co (II) with the planar ligand 6,7-dicycanodipyrido[2,2-d:2',3'-f]quinoxaline (L), [CoL(NO3)2(CH3CN)] (1) has been synthesized and characterized. The crystal structure of the complex was determined by X ray diffraction analysis. The cobalt atom was heptacoordinated to form a distorted pentagonal bipyramid geometry by three nitrogen atoms of L and a CH3CN, four oxygen atoms of two NO3^- in complex 1. Biological tests against four different cell lines (HL-60, KB, Hela and BGC-823) showed that the complex had strong antitumor properties with the 50% inhibition concentrations (IC50) of the complex were in a μmol·L^-1 range. For understanding the antitumor mechanism of the complex, the binding modes of the complex with calf thymus DNA had also been investigated with spectrophotometric methods, viscosity and thermal denaturation measurements. The experimental results indicated that complex 1 intercalated into DNA base pairs. The intrinsic binding constant Kb values for 1 (4.43×10⁵mol·L^-1) and L (1.65×10⁵mol·L^-1) were determined by absorption titration and calculated with the model of McGhee and Von Hippel.

Key words: Cobalt(II)Complex6,7-Dicycanodipyrido[2,2-d:2',3'-f]quinoxaline, Cobalt(II)Complex6,7-Dicycanodipyrido[2,2-d:2',3'-f]quinoxaline, Antitumor activity, Antitumor activity, Crystal structure, Crystal structure, Interaction with DNA, Interaction with DNA

Supporting: This work was supported by National Natural Science Foundation of China (No. 30171107).

徐志栋, 刘河, 王敏, 肖苏龙, 杨铭^*, 卜显和. 具有抗肿瘤活性的6,7-二氰基-二吡啶基[2,2-d:2',3'-f]喹喔啉合钴(II)配合物的合成、晶体结构及与DNA结合的研究[J]. .

Xu Zhidong, Liu He, Wang Min, Xiao Sulong, Yang Ming^*, Bu Xianhe . Cobalt (II) Complex of 6,7-Dicycanodipyridoquinoxaline with Antitumor Activities: Synthesis, Crystal Structure and Binding with DNA[J]. .

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