Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 μΜ to 0.43 μΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor.

中文翻译：

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6-(咪唑并[1,2-a]吡啶-6-基)喹唑啉衍生物通过抑制 PI3Kα 的抗癌剂的设计、合成和生物学评价

磷脂酰肌醇 3-激酶 (PI3K) 信号通路的异常表达通常与肿瘤发生、进展和预后不良有关。因此，PI3K抑制剂在治疗癌症方面引起了极大的兴趣。本研究设计、合成了一系列新的 6-(咪唑并[1,2-a]吡啶-6-基)喹唑啉衍生物，并通过 1H NMR、13C NMR 和 HRMS 光谱分析对其进行了表征。在体外抗癌试验中，大多数合成化合物显示出对各种肿瘤细胞系的亚微摩尔抑制活性，其中 13k 是最有效的化合物，其对所有测试细胞系的 IC50 值范围为 0.09 μM 至 0.43 μM。此外，13k 通过抑制 PI3Kα 诱导 HCC827 细胞 G2/M 期细胞周期停滞和细胞凋亡，IC50 值为 1.94 nM。