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

3 alpha-Methoxyserrat-14-en-21 beta-ol (PJ-1) and 3 beta-methoxyserrat-14-en-21 beta-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 (IC50 = 251),12 (IC50 = 248), and 17 (IC50= 230 mol ratio/32 pmol/TPA), were 2-fold stronger than those of the other compounds such as oleanolic acid (IC50 = 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. (C) 2011 Elsevier Masson SAS. All rights reserved.