A series of novel 4-substituted phthalazinones as Aurora B kinase inhibitors was synthesized and evaluated the anti-proliferative activities against A549, HCT116, MCF-7 and HepG2 cells. 1-(4-(2-((4-Oxo-3,4-dihydrophthalazin-1-yl)amino)ethyl) phenyl)-3-(3-(trifluoromethyl)phenyl)urea (17b) exhibited the most potent anti-proliferative activity against HCT116 cells with IC₅₀ value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC₅₀ value of 142 nM. Furthermore, 17b inhibited the phosphorylation of Aurora B on Thr232, leading to cell cycle arrest in the G2/M phase by down-regulating the expression of CyclinB1 and Cdc2 proteins, and apoptosis by up-regulating the expression of BAD and Bax proteins in HCT116 cells. In addition, a docking study revealed that 17b could form key hydrogen bonds with Ala173, Glu171 and Glu177 in Aurora B. All the results reveal that 17b is worthy of further development as an Aurora B kinase inhibitor.

合成了一系列新型的4-取代的邻苯二氮酮作为Aurora B激酶抑制剂，并评估了其对A549，HCT116，MCF-7和HepG2细胞的抗增殖活性。1-（4-（2-（（4-Oxo-3,4-二氢酞嗪-1-基）氨基）乙基）苯基）-3-（3-（三氟甲基）苯基）脲（17b）显示出最有效的抗具有对HCT116细胞的增殖活性，IC ₅₀值为4.35± 1.21μM ，以及中等的Aurora B抑制活性，IC ₅₀值为142 nM。此外，17b抑制Thr232上Aurora B的磷酸化，通过下调CyclinB1和Cdc2蛋白的表达导致细胞周期停滞在G2 / M期，并通过上调HCT116细胞的BAD和Bax蛋白的表达来凋亡。此外，对接研究显示17b可以与Aurora B中的Ala173，Glu171和Glu177形成关键氢键。所有结果表明17b作为Aurora B激酶抑制剂值得进一步开发。