College of Life Science and Bio-engineering, Beijing University of Technology, Beijing 100124, China.
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Molecules. 2019 Nov 7;24(22):4034. doi: 10.3390/molecules24224034.
In this work, a series of benzylsulfone coumarin derivatives - were synthesized and characterized. Kinase inhibitory activity assay indicated that most of the compounds showed considerable activity against PI3K. Anti-tumor activity studies of the active compounds were also carried out in vitro on the Hela, HepG2, H1299, HCT-116, and MCF-7 tumor cell lines by MTS assay. The structure-activity relationships (SARs) of these compounds were analyzed in detail. Compound exhibited the most potent activities against the mentioned cell lines with IC values ranging from 18.12 to 32.60 μM, followed by with IC values of 29.30-42.14 μM. Furthermore, and clearly retarded the migration of Hela cells in vitro. Next, an in silico molecular docking study was conducted to evaluate the binding models of and towards PI3Kα and PI3Kβ. Collectively, the above findings suggested that compounds and might be promising PI3K inhibitors deserving further investigation for cancer treatment.
在这项工作中，我们合成并表征了一系列苯磺酰基香豆素衍生物。激酶抑制活性测定表明，大多数化合物对 PI3K 表现出相当的活性。对活性化合物的体外抗肿瘤活性研究也在 Hela、HepG2、H1299、HCT-116 和 MCF-7 肿瘤细胞系上通过 MTS 测定进行。详细分析了这些化合物的构效关系（SAR）。化合物 对上述细胞系表现出最强的活性，IC 值范围为 18.12 至 32.60 μM，其次是化合物 ，IC 值为 29.30-42.14 μM。此外，化合物 和 明显抑制了 Hela 细胞的体外迁移。接下来，进行了计算机分子对接研究，以评估 和 与 PI3Kα 和 PI3Kβ 的结合模型。综上所述，这些发现表明，化合物 和 可能是有前途的 PI3K 抑制剂，值得进一步研究用于癌症治疗。
