The synthesis and anti-tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors.
Basic Information
ID: ALA4665819
Journal: Bioorg Med Chem Lett
Title: The synthesis and anti-tumour properties of novel 4-substituted phthalazinones as Aurora B kinase inhibitors.
Authors: Zhang XJ,Xu Y,Mou HX,Wang S,Hao SY,Chen SW
Abstract: 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 IC value of 4.35 ± 1.21 μM, as well as the moderate Aurora B inhibitory activity with the IC 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.
CiteXplore: 32941989
DOI: 10.1016/j.bmcl.2020.127556
Patent ID: ┄