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Design, synthesis and biological evaluation of novel indolin-2-ones as potent anticancer compounds
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2017-06-07 , DOI: 10.1016/j.bmcl.2017.06.019
Andong Zhou , Lei Yan , Fangfang Lai , Xiaoguang Chen , Masuo Goto , Kuo-Hsiung Lee , Zhiyan Xiao

The indolin-2-one core is a privileged structure for antitumor agents, especially kinase inhibitors. Twenty-three novel indolin-2-ones were designed by molecular dissection of the anticancer drug indirubin. Seventeen of them exhibited significant inhibition against the tested cell lines, and two of them (1c and 1h) showed IC50 values at the submicromolar level against HCT-116 cells. Compounds 1c and 2c were also potent inhibitors of the triple-negative breast cancer (TNBC) cell line MDA-MB-231. Flow cytometry was utilized to explore the antitumor mechanism of 1c and 2c with MDA-MB-231 cells, and distinct effects were observed on 2c. Furthermore, immunocytochemical examination of 1c suggested a destabilization of microtubules, which was significantly different from the effect of IM, an indirubin derivative.



中文翻译:

新型吲哚-2-酮类有效抗癌化合物的设计,合成及生物学评价

吲哚-2-酮核是抗肿瘤剂(特别是激酶抑制剂)的优先结构。通过分子解剖抗癌药靛玉红设计了二十三种新型吲哚-2-酮。它们中的十七个对测试的细胞系表现出显着的抑制作用,其中两个(1c1h)显示出对HCT-116细胞亚微摩尔水平的IC 50值。化合物1c2c还是三阴性乳腺癌(TNBC)细胞系MDA-MB-231的有效抑制剂。流式细胞仪用于探讨1c2c对MDA-MB-231细胞的抗肿瘤作用,并在2c上观察到明显的作用。。此外,1c的免疫细胞化学检查显示微管不稳定,这与靛玉红衍生物IM的作用明显不同。

更新日期:2017-06-07
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