A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for
设计了一系列含有亲
水基团的
4-氨基喹唑啉衍
生物,并将其鉴定为有效的Pan-
PI3K
抑制剂。体外抗增殖试验的结果表明,该系列化合物对肿瘤的生长具有较强的抑制作用,尤其是对MCF-7细胞的化合物7b具有抑制作用,而对正常细胞的抑制作用较弱。
PI3K激酶测定法显示7b对三种
PI3K亚型具有很高的活性,其
PIcomole的IC50值为。蛋白质印迹分析表明7b可以剂量依赖性方式降低
磷酸化Akt(S473)。进一步的实验表明7b可以诱导MCF-7细胞凋亡。在7b与
PI3K激酶的对接中发现了四个关键的氢键相互作用。