Structure-activity relationship of 7 flavonoids on recombinant human protein kinase CK2 holoenzyme

To observe the effect of 7 flavonoids on recombinant human protein kinase CK 2 holoenzyme activity and investigate their structure-activity relationship.

Recombinant human protein kinase CK 2 alpha' and beta subunits were mixed at equal molar ratio to reconstitute CK 2 holoenzyme. The CK 2 activity was assayed by detecting incorporation of (32)P of [gamma-(32)P]ATP into the substrate for the inhibitory effect by flavonoids and calculation of IC50 was performed according to probability unit (PROBIT) method.

Myricetin, quercetin, morin, luteolin, kaempferol, apigenin, and chrysin were shown to obviously inhibit recombinant CK 2 holoenzyme activity in a concentration-dependent manner with IC50 values of 1.18, 0.51, 16.16, 0.86, 1.88, 1.72, and 13.63 micromol/L, respectively. Myricetin, quercetin, luteolin, kaempferol, and apigenin were more effective than DRB and A3, which were known as CK 2 inhibitors in vitro. Whereas morin and chrysin displayed a similar effect to DRB. Structure-activity study indicated that the major structural requirements for the potent inhibition of CK 2 by these flavonoids were hydroxyl group at position 6, 3' and 4'. Different from these requirements, absence of a hydroxyl group at position 3 did not modify their inhibitory potency, while addition of hydroxyl groups at positions 2' or 5' was detrimental to the inhibitory effect on CK 2.

The inhibitory effect of flavonoid on protein kinase CK 2 in vitro may be determined by the position of their hydroxyl groups.