Dehydrozingerone analogs and related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen activation assay. Among the 40 synthesized compounds, the prenylated analogs 16 and 34-36 showed the most significant and promising activity (100% inhibition of activation at 1 x 10(3) mol ratio/TPA, and 82-80%, 37-35%, and 13-11% inhibition at 5 x 10(2), 1 x 10(2), and 1 x 10 mol ratio/TPA, respectively) in this screening. Their activity profiles were comparable to those of the reference standard curcumin. While a prenyl moiety conferred potent chemopreventive activity, an extended prenyl unit such as a farnesyl moiety did not improve activity. Because in vitro inhibitory effects in this assay generally correlate well with in vivo inhibitory effects on tumor promotion, our results strongly suggested that prenylated 16 and 34-36 are likely to be promising antitumor promoters.