多靶点有机金属芳环钌基抗肿瘤化合物的合成与性质分析.pdfVIP

的抑制活性。采用流式细胞术对化合物W3 诱导细胞凋亡能力进行 测定。采用飞行时间-二次离子质谱对化合物W1 、W2 和W3 在细 胞中的分布进行成像。采用荧光滴定对化合物W1 和W3 与DNA 作用机理进行研究。采用计算机模拟方法对化合物和EGFR 的作用 机理进行研究。实验证明所合成化合物W1  W5 均有较好的EGFR 抑制活性，多数化合物对五种肿瘤细胞株有良好的生长抑制作用， 化合物W3 具有较强的诱导细胞凋亡能力，主要分布在细胞线粒体 内，和DNA 之间有较强的小沟结合能力，证实了化合物W3 具有 多靶点的抗肿瘤活性。 关键词：多靶点；抗肿瘤药物；计算机模拟；分子作用机理。 Synthesis and Action of Organometallic Ruthenium Complexes as Multi-targeted Anticancer Agents Abstract Cancer is one of the most severe threat to human health. Nowadays some chemical drugs of tumor treatment were limited by high side effects and poor water solubility. So novel antitumor drugs with high efficacy and low toxicity have drawn more attention. Meanwhile, as the malignant tumor is a kind of multigenic diseases, single targeted antitumor drugs usually lead to drug resistance . Therefore, multi-targeted anticancer agents are the promising direction of the development of antitumor drugs in the future. On the other hand, high throughput screening based on the molecular biology, cell biology and the computer-assisted simulation have occupied an important position in this research field. The application of such technologies can significantly enhance the efficiency of drug discovery and greatly reduce the time for new drug research. In this work, we synthesized eight EGFR inhibitors and five multi-targeted antitumor Ruthenium complexes, followed by the study of biological activity and the hydrolysis properties, interactions with DNA of multi-targeted antitumor compounds. The research results are given as followings: (1) We designed, synthesizeed eight EGFR inhibitors containing 4-anilinoquinazolines and choose four to synthesize five multi-targeted antitumor Ruthenium