Inhibitory effects of dehydrozingerone and related compounds on 12-O-tetradecanoylphorbol-13-acetate induced Epstein–Barr virus early antigen activation

Dehydrozingerone, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, is half an analog of curcumin which is known to have anti-tumor activity. The anti-tumor promoting activity of dehydrozingerone was evaluated by determining the inhibitory effect on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The concentration needed for 50% inhibition of the tumor promotion (IC50) of dehydrozingerone was similar to that of curcumin. To elucidate the structure–activity relationship on the anti-tumor promoting activity, dehydrozingerone, curcumin, isoeugenol, which has no carbonyl group in the side chain, benzalacetone, which is the basic structure of dehydrozingerone, o-dehydrozingerone, which is the ortho-hydroxyl substituted compound of dehydrozingerone, and their related compounds were investigated using the in vitro short-term assay on TPA-induced EBV-EA activation. o-Dehydrozingerone showed the most potent inhibitory effect in a series of tested dehydrozingerone derivatives and their related monosubstituted benzalacetones. This suggests that the occupation at both ortho positions of the hydroxyl group enhances the anti-tumor promoting activity. Isoeugenol inhibited the tumor promoting activity at a concentration of about one-third of the IC50 of dehydrozingerone. This indicates that the carbonyl group in the side chain has a negative impact on the anti-tumor promoting activity. The inhibitory effects of the carbon–carbon bond in the side chain were studied using benzylacetone with a single bond, benzalacetone with a double bond and 4-phenyl-3-butyn-2-one with a triple bond. 4-Phenyl-3-butyn-2-one inhibited the most potent activity followed by benzalacetone and benzylacetone.