A new family of densely functionalized fused-benzoquinones as potent human protein kinase CK2 inhibitors

摘要

Abstract A new series of 2-amino-4-phenyl-6-hydroxy-7-alkyl-pyranobenzoquinones was synthesized as ATP-competitive CK2 inhibitors. They were readily synthesized through a three-component Knoevenagel condensation-Michael addition-heterocyclization reaction from aldehydes, malononitrile, and 3-alkyl-2,5-dihydroxybenzoquinones. Some of the synthesized compounds presented interesting inhibitory activity with IC 50 values in the submicromolar range. A structure-activity relationship study was carried out and the mode of binding was analysed by docking studies and supported by ATP competition assays. Graphical abstract Display Omitted Highlights ? A new series of densely functionalized fused-benzoquinones was synthesized through a straight three-component reaction. ? Some compounds showed CK2 inhibition with IC 50 values in the submicromolar range. ? Structure-activity relationships were outlined. ? The binding pattern was analysed by molecular docking, and corroborated by ATP competition assay.