取代的 3-(5-咪唑并[2,1-b]噻唑基亚甲基)-2-吲哚啉酮及其类似物：合成、细胞毒性活性及作用机制研究。
Substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues: synthesis, cytotoxic activity, and study of the mechanism of action.
机构信息
Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
出版信息
J Med Chem. 2012 Mar 8;55(5):2078-88. doi: 10.1021/jm2012694. Epub 2012 Feb 15.
Abstract
The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
摘要
报告了取代的 3-(5-咪唑并[2,1-b]噻唑基亚甲基)-2-吲哚啉酮及其类似物的合成。根据马里兰州贝塞斯达国立癌症研究所（NCI）提供的方案，评估了它们的细胞毒性活性。选择的化合物的作用被检查，以比较与有效的秋水仙碱位点剂 combretastatin A-4 的微管组装的潜在抑制作用。最有效的化合物也强烈和选择性地抑制了癌细胞中癌蛋白激酶 Akt 的磷酸化。最有趣的化合物的作用被检查对 HT-29 结肠癌细胞的生长的影响。这些化合物使细胞停滞在细胞周期的 G2/M 期，正如微管组装抑制剂所预期的那样。
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