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.