Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus activation assay

In a search for anti-tumor-promoting agents, we carried out a primary screening of twenty-nine 8-substituted and four 6-substituted derivatives of 7-methoxycoumarins isolated from plants of the Murraya and/or Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. This investigation indicated that the prenyl (3-methyl-2-butenyl) or 2-hydroxy-3-methylbutyl (or butenyl) unit as an isoprenoid moiety at C-8 on the 7-methoxycoumarin nucleus plays an important role in the anti-tumor-promoting activity. Some of the 8-substituted 7-methoxycoumarins isolated from Murraya species, murrangatin (7), minumicrolin (10) and chloticol (18), were found to significantly inhibit EBV-EA activation, and preserved the high viability of Raji cells, suggesting that 7, 10 and 18 might be valuable anti-tumor-promoting agents.