药物配合物修饰Keggin型多酸复合物的组装化学

发布时间：2019-04-02 04:25

【摘要】：目的设计合成出的新的药物配合物修饰Keggin型多酸的复合物，对其进行结构表征及抗肿瘤活性研究。探索复合物的合成规律，研究其构效关系。方法复合物的合成采用水热合成法；通过X-射线单晶衍射、X-射线粉粉末衍射、元素分析、差热-热重和红外光谱等方法对晶体进行结构表征。利用MTT法研究新型复合物的体外抗肿瘤活性(SG7901胃癌细胞株、SMMC7721肝癌细胞株)。结果合成出4个新型的药物配合物修饰Keggin型多酸复合物。体外抗肿瘤实验显示，不同结构的复合物体现出不同程度的抗肿瘤活性和选择性。最后计算得到相应的IC50值。结论本论文选择喹诺酮类药物分子作为有机配体，用不同过渡金属离子来修饰或者桥连多酸，通过分子自组装构筑了4个新型的药物多酸复合物： [Cu2(Enro)3H2O][SiW12O40]·H2O (1)； {[Cu(Norf)2]}2[SiW12O40](2)； H2[Ni(Enro)2][SiW12O40]·(Enro)2·2H2O (3)； H4[Ni(Enro)2(H2O)2](β-Mo8O26) H2O (4)。体外抗SGC7901肿瘤细胞和SMMC7721肿瘤细胞表明，Keggin型H4SiW12O40母体化合物对上述两种肿瘤没有抑制活性，通过金属药物配合物修饰后，铜-喹诺酮配合物对于多酸的抗肿瘤活性影响较小，，而镍-喹诺酮配合物对于多酸的抗肿瘤活性影响较大，说明金属离子对于电子在多酸与金属配合物的转移起到了关键作用。同样化合物4的抗肿瘤活性结果也表现出同样的效应。
[Abstract]:Aim to design and synthesize a novel drug complex modified with Keggin type polyacid complex and to study its structure characterization and antitumor activity. The synthesis rule and structure-activity relationship of the complexes were studied. Methods the complex was synthesized by hydrothermal synthesis and characterized by X-ray single crystal diffraction, X-ray powder diffraction, elemental analysis, DTA-TG and IR spectra. The antitumor activity of the novel complex in vitro (SG7901 gastric cancer cell line and SMMC7721 hepatoma cell line) was studied by MTT assay. Results four novel drug complexes modified Keggin type polyacid complexes were synthesized. Anti-tumor experiments in vitro showed that the complexes with different structures showed different degree of antitumor activity and selectivity. Finally, the corresponding IC _ (50) values are calculated. Conclusion in this paper, quinolones are selected as organic ligands, and different transition metal ions are used to modify or bridge polyacids. Four novel drug polyacid complexes were synthesized by molecular self-assembly: [Cu2 (Enro) 3H2O] [SiW12O40] H2O (1); {[Cu (Norf) 2]} 2 [SiW12O40] (2); H2 [Ni (Enro) 2] [SiW12O40] (Enro) 2 路2H2O (3); H4 [Ni (Enro) 2 (H2O) 2] (尾-Mo8O26) H2O (4). In vitro anti-SGC7901 tumor cells and SMMC7721 tumor cells showed that Keggin-type H4SiW12O40 parent compounds had no inhibitory effect on the above two kinds of tumors. After modified by metal drug complexes, copper-quinolone complexes had little effect on the antitumor activities of polyacids. Nickel-quinolone complexes have a great effect on the antitumor activity of polyacids, indicating that metal ions play a key role in the transfer of electrons between polyacids and metal complexes. The antitumor activity of the same compound 4 showed the same effect.
【学位授予单位】：佳木斯大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914

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