Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds

Abstract

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by 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. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1–3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3′,3′-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of β-carotene, a well-known anti-tumor promoter. Furthermore, the structure–activity correlation of porritoxins and their related compounds were discussed.

Keywords:

• Porritoxin
• Isoindolinone
• Phthalide
• Alternaria porri
• Anti-tumor promoter
• Epstein-Barr virus early antigen

Acknowledgements

We thank E. Nishikawa at Doshisha Women's College of Liberal Arts for preparing natural compounds. This study was supported in part by a Grant from the Ministry of Education, Science, Sports and Culture of Japan, and also Grants from the National Cancer Institute (CA 17625).