J. Med. Chem.：一类化合物具较好抗微管聚集作用
2011-11-06 07:00 · wind来自中科院上海药物研究所的两个研究组合作发现了一类2,4,5-三取代嘧啶类化合物具有较好的抗微管聚集作用，国家自然科学基金及上海市科技委员会的支持。
文章的通讯作者是上海药物研究所药物化学胡有洪研究员与药理学楼丽广研究员，目前这一化合物正在进行成药性和深入的药效学评价阶段，（生物探索）
相关英文论文摘要：
Synthesis and Biological Evaluation of 2,4,5-Substituted Pyrimidines as a New Class of Tubulin Polymerization Inhibitors
Members of a series of 2,4,5-substituted pyrimidine derivatives were synthesized, and their interactions with tubulin and their antiproliferative activities against the human hepatocellular carcinoma cells of liver (BEL-7402) were evaluated. One member of this family, the indole-pyrimidine 4k, having an indole-aryl-substituted aminopyrimidine structure, was observed to be an excellent inhibitor of tubulin polymerization (IC50 = 0.79 μM) and to display significantly high antiproliferative activities against several cancer cell lines with IC50 values ranging from 16 to 62 nM. This substance displayed a high propensity to arrests cells at the G2/M phase of the cell cycle (EC50 = 20 nM). In addition, 4k was found to competitively inhibit colchicine binding to tubulin, indicating that it binds to the colchicine-binding site of tubulin. The observations made in this investigation demonstrate that 2,4,5-substituted pyrimidines represent a new class of tubulin polymerization inhibitors with significant antiproliferative activity.
英文论文链接：https://pubs.acs.org/doi/abs/10.1021/jm101388d
微管具有多种重要的生物学功能，由于微管在细胞生长和发育过程中的重要作用，此类化合物可以引起细胞发生G2/M期周期阻滞（EC50 = 20 nM），在分子水平和细胞水平上均表现出明显的抗微管聚集作用(IC50 = 0.79 μM)，有望开发成为新的抗肿瘤药物。结构优化和构效关系分析，
来自中科院上海药物研究所的两个研究组合作发现了一类2,4,5-三取代嘧啶类化合物具有较好的抗微管聚集作用，因此，
此类化合物为新的微管蛋白抑制剂，有望开发成为新的抗肿瘤药物。发现了一类2,4,5-三取代嘧啶类化合物具有较好的抗微管聚集作用。活性优于阳性对照秋水仙碱(IC50 = 2.68 μM)。
上海药物研究所研究人员致力于微管蛋白抑制剂的研究，