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One hundred and fifteen synthesized mono, di, and trihydroxybenzamide and thiobenzamide derivatives having structures related to euglobals were 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-trihydroxybenzamide and 3-acyl-2,4,6-trihydroxythiobenzamide derivatives exhibited strong or moderate activities, and the latter compounds were less cytotoxic than the former. Meanwhile, little or no activity was observed with mono and dihydroxybenzamide and dihydroxythiobenzamide derivatives. Structural requirements for the activities of these compounds have been discussed in detail. Among the above compounds, compounds 36 and 73, which were significantly active on the inhibition of EBV activation, were investigated using a two-stage mouse skin carcinogenesis test induced by 7,12-dimethylbenz[a]anthracene (DMBA) and TPA. The results of the in vivo test showed that both compounds have a stronger inhibitory effect than that of the well-known anti-tumor-promoter, glycyrrhetic acid. These results suggested that the two compounds might be valuable as anti-tumor-promoters in chemical carcinogenesis.

biological and pharmaceutical bulletin

Inhibitors of Skin-Tumor Promotion. XIII. Inhibitory Effects of Euglobals and Their Related Compounds on Epstein-Barr Virus Activation and on Two-Stage Carcinogenesis of Mouse Skin Tumors. (2).