INHIBITORS OF SKIN-TUMOR PROMOTION .13. INHIBITORY EFFECTS OF EUGLOBALS AND THEIR RELATED-COMPOUNDS ON EPSTEIN-BARR-VIRUS ACTIVATION AND ON2-STAGE CARCINOGENESIS OF MOUSE SKIN TUMORS .2.

One hundred and fifteen synthesized mono, di, and trihydroxybenzamide and thiobenzamide derivatives having structures related to euglobals w ere examined for their inhibitory effects on Epstein-Barr virus (EBV) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) as a primary screening test for anti-tumor-promoters. In general, 3-acyl-2,4,6-trih ydroxybenzamide and 3-acyl-2,4,6-trihydroxythiobenzamide derivatives e xhibited strong or moderate activities, and the latter compounds were less cytotoxic than the former. Meanwhile, little or no activity was o bserved with mono and dihydroxybenzamide and dihydroxythiobenzamide de rivatives. Structural requirements for the activities of these compoun ds have been discussed in detail. Among the above compounds, compounds 36 and 73, which were significantly active on the inhibition of EBV a ctivation, were investigated using a two-stage mouse skin carcinogenes is test induced by 7,12-dimethylbenz[a]anthracene (DMBA) and TPA. The results of the in Five test showed that bath compounds have a stronger inhibitory effect than that of the well-known anti-tumor-promoter, gl ycyrrhetic acid. These results suggested that the two compounds might be valuable as anti-tumor-promoters in chemical carcinogenesis.