Effect and structure-activity study of nine kinds of anthraquinone derivatives on recombinant human protein kinase CK2 holoenzyme

Abstract

Aim: To observed the effects of nine kinds of anthraquinone derivatives on recombinant human protein kinase CK2 holoenzyme activity and investigated their structure-activity relationships. Methods: Recombinant human protein kinase CK2α′ and β subunits were mixed at equal molar ratio to reconstitute CK2 holoenzyme. The CK2 activity was assayed by detecting incorporation of 32P of [γ-32 P] ATP into the substrate for the inhibitory effect by anthraquinone derivatives. Calculation of IC50 values was performed according to the law of semi-effect-probit. Results: Mitoxantrone, anthraquinone-2-carboxylic acid, 1, 2-diaminoanthraquinone, 1, 8-dihydroxyanthraquinone and quinizarin were shown to inhibit obviously recombinant CK2 holoenzyme activity in a concentration-dependent manner with IC50 values of 0.66 inverted commas 0.81 inverted commas 8.81 inverted commas 28.76 and 61.26 μmol·L-1, respectively; among that mitoxantrone, anthraquinone-2-carboxylic acid and 1, 2-diaminoanthraquinone were more effective than DRB and A3, which were known as CK2 inhibitors in vitro. However, 1-aminoanthraquinone and 1-chloroanthraquinone undergo a drop in inhibitory efficiency, with IC50 values of 143.38, 221.18 μmol·L-1, respectively. While anthraquinone and 2-ethylanthraquinone did not change the CK2 activity fundamentally. Structure-activity study indicated that the major structural requirements for the potent inhibition of CK2 by anthraquinone-2-carboxylic acid, 1,8-dihydroxyanthraquinone and 1, 2-diaminoanthraquinone were carboxy group at position 2, hydroxyl group at position 8 and amino group at position 2, respectively. Differ from these requirements, as 2-ethylanthraquinone absence of a ethyl group at position 2 and 1-chloroanthraquinone absence of a chlorine group at position 1 did not modify their inhibitory potency. Conclusion: Mitoxantrone, anthraquinone-2-carboxylic acid and 1, 2-diaminoanthraquinone were three stronger inhibitors of recombinant human protein kinase CK2 in vitro.