基于羧酸修饰的含硫吡啶金属化合物的合成及活性研究

G-quadruplex DNA dose exist in most important positions of human genes, which is a good target for antitumor drugs. It is helpful to develop new metal antitumor agents by studying metal complexes acting on G-quadruplex DNA with high and specific antitumor activity. In this project, a series of carboxyl sulfur-containing pyridine ligands were design and the reactions of these ligands with metal ions with anticancer activity will be investigated. The relationship of structure-properties-bioactivity of these metal complexes will be carried out via the comprehensive application of biological and chemical methods. The ability of these ligands and their metal complexes to induce the formation of G-quadruplex, the interaction and the binding mode between these metal complexes and G-quadruplex, and the stability of the G-quadruplex will be studied via UV-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism et al. NMR spectroscopy and X-ray spectroscopy can also be used to obtain detailed structural information on the interactions occurring between these metal complexes and G-quadruplex. The influence of the position of substituents, the stereo effect, electronic effect on the structure and properties of these metal complexes will be analyzed, and the possibility of such metal complexes as the potential anticancer drugs will also be explored.

DNA的二级特殊结构G-四链体存在于人体基因组的一些重要位置，是很好的肿瘤药物作用靶点。研究作用于G-四链体的小分子金属配合物，寻找具有较高抗肿瘤活性和高效选择性的金属配合物将有助于开发新型金属抗肿瘤药物。本项目设计合成一系列羧酸修饰的含硫吡啶配体，并将这些配体与具有抗肿瘤活性的贵金属离子和其他过渡金属离子反应合成金属配合物。综合利用化学和生物学的方法研究金属配合物的结构-性质-生物活性之间的关系，通过紫外可见吸收光谱法、荧光光谱法、圆二色谱法、核磁、X-射线单晶衍射等手段研究金属配合物诱导产生G-四链体的能力、与G-四链体的作用、结合模式以及对G-四链体结构的稳定能力。考察配体上取代基的位置、体积大小、电子效应等对金属配合物的结构和性质的影响，探索此类金属配合物作为抗肿瘤药物的可能性。

功能金属-有机配合物在抗肿瘤药物、光催化、发光及磁性材料等方面有重要的应用价值。本项目设计合成了一系列羧酸/膦酸修饰的苯并咪唑、吡啶、咔唑、芴等有机配体，并将这些配体与金属离子反应合成金属配合物。综合利用配位化学和无机药物化学等理论和技术研究了部分金属配合物的结构-性质之间的关系，通过紫外可见吸收光谱法、荧光光谱法、X-射线单晶衍射、琼脂糖凝胶电泳等手段研究金属配合物的结构和性质，用MTT法考察部分化合物对不同肿瘤细胞的抑制作用，探索此类金属配合物作为抗肿瘤药物的可能性。还对部分化合物的光催化能力、发光及磁性质进行研究，考察配体上取代基的位置、体积大小等对金属配合物的结构和性质的影响，为这些化合物作为新颖功能材料提供了理论依据。