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

Abstract 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 (IC 50  = 330 mol ratio/32 pmol/TPA), 9 (IC 50  = 335), 10 (IC 50  = 338), and 15 (IC 50  = 350) were stronger than those of the other compounds and the positive control, oleanolic acid (IC 50  = 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.