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

3α-Methoxyserrat-14-en-21β-ol (1) and 3β-methoxyserrat-14-en-21β-ol (2) and their conjugates with curcumin, kojic acid, quercetin, and baicalein (3–18), as well as new analogs (19–24) derived from 1 and 2, 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 16 (IC50 = 330 mol ratio/32 pmol/TPA), 9 (IC50 = 335), 10 (IC50 = 338), and 15 (IC50 = 350) were stronger than those of the other compounds and the positive control, oleanolic acid (IC50 = 449). Compounds 15 and 16, which are conjugates of one molecule each of 1 or 2 and quercetin, 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.

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