Conjugates of 3α-methoxyserrat-14-en-21β-ol (PJ-1) and 3β-methoxyserrat-14-en-21β-ol (PJ-2) as cancer chemopreventive agents.

Abstract 3α-Methoxyserrat-14-en-21β-ol ( PJ-1 ) and 3β-methoxyserrat-14-en-21β-ol ( PJ-2 ) were conjugated with well-known phenolic compounds, narigenin, hesperetin, genistein, and daidzein ( 1 – 8 ). Other conjugates of PJ-2 –3,5-dihydroxy-4-methoxybenzoic acid ( 9 ), PJ-2 –pyrogallol ( 10 ), and derivatives of PJ-1 , PJ-2 –3,3-dimethyl-succinates ( 11 , 12 ), PJ-1 , PJ-2 –succinates ( 13 , 14 ), PJ-2 –glycine ( 15 ), PJ-2 –piperidine acetic acid ( 16 ), and PJ-1 epoxy –3,3-dimethyl-succinate ( 17 ) were tested for their inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12- O -tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 11 (IC 50  = 251), 12 (IC 50  = 248), and 17 (IC 50  = 230 mol ratio/32 pmol/TPA), were 2-fold stronger than those of the other compounds such as oleanolic acid (IC 50  = 449). Compounds 10 , 11 , and 17 inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse-skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.