Cancer chemopreventive effect of quassinoid derivatives. Introduction of side chain to shinjulactone C for enhancement of inhibitory effect on Epstein-Barr virus activation.

A series of shinjulactone C (1) derivatives (2-8) were synthesized and evaluated for their anti-tumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The succinate and 3',3'-dimethylsuccinate derivatives of 1 exhibited higher inhibitory effects than 1. From the point of view of structure-activity relationships, the succinate derivatives (2, 4) demonstrated better potency than the glutarate derivatives (3, 5-8). As substituted moieties of 3'-position became bulky, the inhibitory effects of the glutarate derivatives (7, 8) significantly decreased.