Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan.
Invest New Drugs. 2012 Feb;30(1):164-75. doi: 10.1007/s10637-010-9547-7. Epub 2010 Oct 2.
Designed from a high throughput screened hit compound, novel 2-amino-1-thiazolyl imidazoles were synthesized and demonstrated cytotoxicity against human cancer cells. 1-(4-Phenylthiazol-2-yl)-4-(thiophen-2-yl)-1H-imidazol-2-amine (compound 2), a 2-amino-1-thiazolyl imidazole, inhibited tubulin polymerization, interacted with the colchicine-binding sites of tubulins, and caused cell cycle arrest at the G(2)/M phase in human gastric cancer cells. Disruption of the microtubule structure in cancer cells by compound 2 was also observed. Compound 2 concentration-dependently inhibited the proliferation of cancer cells in histocultured human gastric and colorectal tumors. Given orally, compound 2 prolonged the lifespans of leukemia mice intraperitoneally inoculated with the murine P388 leukemic cells. We report 2-amino-1-thiazolyl imidazoles as a novel class of orally active microtubule-destabilizing anticancer agents.
从高通量筛选的命中化合物设计出发，合成了新型 2-氨基-1-噻唑基咪唑并化合物，并证明其对人癌细胞具有细胞毒性。1-(4-苯基噻唑-2-基)-4-(噻吩-2-基)-1H-咪唑-2-胺（化合物 2）是一种 2-氨基-1-噻唑基咪唑并化合物，它抑制微管蛋白聚合，与微管蛋白的秋水仙碱结合部位相互作用，并导致人胃癌细胞的细胞周期停滞在 G(2)/M 期。还观察到化合物 2 破坏癌细胞中的微管结构。化合物 2 浓度依赖性地抑制组织培养的人胃和结直肠肿瘤中癌细胞的增殖。口服给予化合物 2 可延长经腹腔接种小鼠 P388 白血病细胞的白血病小鼠的寿命。我们报告 2-氨基-1-噻唑基咪唑并化合物是一类新型具有口服活性的微管不稳定的抗癌药物。
