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.
Ito
C
C
Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan.
Itoigawa
M
M
Furukawa
H
H
Tokuda
H
H
Okuda
Y
Y
Mukainaka
T
T
Okuda
M
M
Nishino
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014775:Virus Activation / Q000187:drug effects
D000970:Antineoplastic Agents; D003374:Coumarins; D013755:Tetradecanoylphorbol Acetate