Antitumor‐Promoting Effects and Cytotoxic Activities of Dammar Resin Triterpenoids and Their Derivatives
Antitumor‐Promoting Effects and Cytotoxic Activities of Dammar Resin Triterpenoids and Their Derivatives
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达玛树脂三萜类化合物及其衍生物的抗肿瘤促进作用和细胞毒活性
DOI：
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发表时间：
2010
影响因子：
2.9
通讯作者：
T. Akihisa
中科院分区：
文献类型：
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作者：
M. Ukiya;Takashi Kikuchi;H. Tokuda;K. Tabata;Y. Kimura;Takanari Arai;Y. Ezaki;Osamu Oseto;Takashi Suzuki;T. Akihisa
从爪哇沙姜（Shorea javanica K.）& V.（Dipterocarpaceae）.其中一种酸性三萜类化合物达玛烯醇酸（1）被转化为14种衍生物，即醇21、醛22和12种L-氨基酸缀合物23-34。检查化合物1-34对Raji细胞中12-O-十四酰基佛波醇13-乙酸酯（TPA）诱导EB病毒早期抗原（EBV-EA）的抑制作用，这是已知的抗肿瘤启动子的初步筛选试验。除了化合物4、5、12-14、16和17之外，所有测试的化合物均显示出对EBV-EA活化的抑制作用，其效力与β-胡萝卜素（一种已知的天然抗肿瘤促进剂）相当或更强。此外，在以7，12-二甲基苯并[a]蒽（DMBA）为引发剂、TPA为促进剂的体内两阶段小鼠皮肤致癌试验中，（20 S）-20-羟基-3，4-断达玛-4（28），24-二烯-3-醛（22）对皮肤肿瘤促进具有抑制作用。此外，化合物1-34对人癌细胞系的细胞毒性活性的评价显示，21和22）或与L-氨基酸缀合（即，23-34）增强了对人黑素瘤细胞系CRL 1579的细胞毒性。
Nineteen known triterpenoids, 1–19, and one known sesquiterpenoid, 20, were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid (1), was converted to fourteen derivatives, namely, an alcohol, 21, an aldehyde, 22, and twelve L‐amino acid conjugates, 23–34. Compounds 1–34 were examined for their inhibitory effects on the induction of Epstein–Barr virus early antigen (EBV‐EA) by 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12–14, 16, and 17, showed inhibitory effects against EBV‐EA activation with potencies either comparable with or stronger than that of β‐carotene, a known natural antitumor promoter. In addition, (20S)‐20‐hydroxy‐3,4‐secodammara‐4(28),24‐dien‐3‐al (22) exhibited inhibitory effects on skin tumor promotion in an in vivo two‐stage mouse skin carcinogenesis test based on 7,12‐dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1–34 against human cancer cell lines showed that reduction (i.e., 21 and 22) or conjugation with L‐amino acids (i.e., 23–34) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.
影响因子：
1.7
作者：
Akihisa, T;Tokuda, H;Nishino, H
通讯作者：
Nishino, H