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- is half an analo g of curcumin which is known to have anti-tumor activity. The anti-tumor pr omoting activity of dehydrozingerone was evaluated by determining the inhib itory effect on Epstein-Barr virus early antigen (EBV-EA) activation induce d by 12-O-tetradecanoylphorbol-13-acetate (TPA). The concentration needed f or 50% inhibition of the tumor promotion (IC50) Of dehydrozingerone was sim ilar to that of curcumin. To elucidate the structure-activity relationship on the anti-tumor promoting activity, dehydrozingerone, curcumin, isoeugeno l, which has no carbonyl group in the side chain, benzalacetone, which is t he basic structure of dehydrozingerone, o-dehydrozingerone, which is the or tho-hydroxyl substituted compound of dehydrozingerone, and their related co mpounds were investigated using the in vitro short-term assay on TPA-induce d EBV-EA activation. o-Dehydrozingerone showed the most potent inhibitory e ffect in a series of tested dehydrozingerone derivatives and their related monosubstituted benzalacetones. This suggests that the occupation at both o rtho positions of the hydroxyl group enhances the anti-tumor promoting acti vity. 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 p romoting activity. The inhibitory effects of the carbon-carbon bond in the side chain were studied using benzylacetone with a single bond, benzalaceto ne with a double bond and 4-phenyl-3-butyn-2-one with a triple bond. 4-Phen yl-3-butyn-2-one inhibited the most potent activity followed by benzalaceto ne and benzylacetone. (C) 1998 Elsevier Science Ireland Ltd. All rights res erved.