Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Eur J Med Chem. 2011 Aug;46(8):3368-75. doi: 10.1016/j.ejmech.2011.04.062. Epub 2011 May 10.
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.
3α-甲氧基-14-烯-21β-醇（PJ-1）和 3β-甲氧基-14-烯-21β-醇（PJ-2）与众所周知的酚类化合物橙皮素、柚皮素、染料木黄酮和大豆苷元（1-8）结合。PJ-2-3,5-二羟基-4-甲氧基苯甲酸（9）、PJ-2-没食子酸（10）以及 PJ-1、PJ-2-3,3-二甲基琥珀酸酯（11、12）、PJ-1、PJ-2-琥珀酸酯（13、14）、PJ-2-甘氨酸（15）、PJ-2-哌啶乙酸（16）和 PJ-1 环氧化物-3,3-二甲基琥珀酸酯（17）的其他轭合物也被测试了其对 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的 Epstein-Barr 病毒早期抗原（EBV-EA）激活的抑制作用。11（IC50=251）、12（IC50=248）和 17（IC50=230 摩尔比/32 皮摩尔/TPA）的抑制作用比其他化合物（如齐墩果酸，IC50=449）强 2 倍。化合物 10、11 和 17 在体内两阶段致癌模型中抑制了小鼠皮肤肿瘤的促进作用。体内两阶段小鼠皮肤致癌试验采用 7,12-二甲基苯并[a]蒽（DMBA）作为起始剂，TPA 作为促进剂。
