Design of radiosensitizers targeting for glycolysis of hypoxic tumor based on tumor implanted chick embryo

本研究的目的是开发“硝基唑修饰的葡萄糖型放射增敏剂”，使葡萄糖作为糖酵解系统的底物具有放射增敏活性基团，并注意到缺氧癌细胞依赖于糖酵解系统。作为研究内容，设计合成了乙酰葡萄糖修饰的2-硝基咪唑TX-2244及其5个衍生物，并利用肿瘤细胞和肿瘤植入的鸡蛋模型分析了其放射增敏活性及其增强机制。结果表明，TX-2244通过抑制细胞内葡萄糖摄取，降低细胞内NADH(s)水平，增加辐射对DNA的损伤，显示出较高的辐射致敏活性。

The purpose of this research is the development of the "nitroazole-modified glucose type radiosensitizers" which gave the radiosensitizing active group to glucose used as the substrate of a glycolytic system paying attention to the hypoxic cancer cell being dependent on a glycolytic system. As contents of the research, the design and synthesis of acetylglucose-modified 2-nitroimidazole TX-2244 and its five derivatives were done, and analysis of radiosensitizing activity and its enhancing mechanism was conducted using tumor cells and a tumor-implanted chicken egg model. It was shown clearly that TX-2244 demonstrates high radiosensitizing activity as an obtained result through the prevention of intracellular uptake of glucose, the decrease of the level of intracellular NADH(s), and increase of DNA damage by radiation.