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

In a search for anti-tumour-promoting agents, we carried out a primary scre ening 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 vir us early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-1 3-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 is oprenoid 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-meth oxycoumarins isolated from Murraya species, murrangatin (7), minumicrolin ( 10) and chloticol (18), were found to significantly inhibit EBV-EA activati on, and preserved the high viability of Raji cells, suggesting that 7, 10 a nd 18 might be valuable anti-tumor-promoting agents. (C) 1999 Elsevier Scie nce Ireland Ltd. All rights reserved.