3α-甲氧基-14-齐墩果烯-21β-醇（PJ-1）和 3β-甲氧基-14-齐墩果烯-21β-醇（PJ-2）及其各种抗氧化剂的混合物作为癌症化学预防剂。

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

机构信息

Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

出版信息

Eur J Med Chem. 2010 Jun;45(6):2191-7. doi: 10.1016/j.ejmech.2010.01.057. Epub 2010 Jan 29.

DOI:10.1016/j.ejmech.2010.01.057

PMID:20153563

Abstract

3alpha-methoxyserrat-14-en-21beta-ol (1) and 3beta-methoxyserrat-14-en-21beta-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.

摘要

3α-甲氧基-14-烯-21β-醇（1）和 3β-甲氧基-14-烯-21β-醇（2）及其与姜黄素、曲酸、槲皮素和黄芩素（3-18）的轭合物，以及源自 1 和 2 的新类似物（19-24），都被测试了其对 12-O-十四烷酰佛波醇-13-醋酸酯（TPA）诱导的 Epstein-Barr 病毒早期抗原（EBV-EA）激活的抑制作用。16（IC50=330 摩尔比/32 pmol/TPA）、9（IC50=335）、10（IC50=338）和 15（IC50=350）的抑制作用强于其他化合物和阳性对照齐墩果酸（IC50=449）。15 和 16 是 1 或 2 与槲皮素的单分子轭合物，它们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。