论文部分内容阅读
以噻唑烷酮化合物为例,介绍了先导化合物的研发过程。运用组合化学的方法设计并合成了小分子化合物库,用以发现和优化先导化合物。用肺癌细胞、抗药性肺癌细胞和正常细胞进行高通量筛选,发现了选择性杀伤抗药性肺癌细胞的化合物。作用机制研究表明活性化合物抑制微管蛋白,将细胞阻滞在G2/M期且可诱导细胞凋亡和自噬,其抗癌活性不依赖于P-糖蛋白。这类先导化合物具有良好的细胞膜通透性,体内试验表明其可有效抑制肿瘤的生长。对60个人体肿瘤细胞系的筛选中,发现这类先导化合物具有广谱的抗癌活性,将在未来癌症治疗研究中起到重要的作用。
Taking thiazolidinone compound as an example, the development process of lead compound is introduced. The use of combinatorial chemistry has led to the design and synthesis of small molecule libraries to discover and optimize lead compounds. High-throughput screening of lung cancer cells, drug-resistant lung cancer cells, and normal cells has led to the discovery of compounds that selectively kill resistant lung cancer cells. Studies on the mechanism of action show that the active compounds inhibit tubulin, block cells in the G2 / M phase and induce apoptosis and autophagy, and their anticancer activity is independent of P-glycoprotein. Such lead compounds have good cell membrane permeability, in vivo tests show that it can effectively inhibit tumor growth. Screening of 60 human tumor cell lines, these lead compounds have been found to have a broad spectrum of anticancer activity that will play an important role in the future of cancer therapy research.