Synthesis of the conjugated trienes 5E,7E,9E,14Z,17Z-eicosapentaenoic acid and 5Z,7E,9E,14Z,17Z-eicosapentaenoic acid, and their induction of apoptosis in DLD-1 colorectal adenocarcinoma cells
Synthesis of the conjugated trienes 5E,7E,9E,14Z,17Z-eicosapentaenoic acid and 5Z,7E,9E,14Z,17Z-eicosapentaenoic acid, and their induction of apoptosis in DLD-1 colorectal adenocarcinoma cells
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共轭三烯5E,7E,9E,14Z,17Z-二十碳五烯酸和5Z,7E,9E,14Z,17Z-二十碳五烯酸的合成及其对DLD-1结直肠腺癌细胞凋亡的诱导
作者：
T. Tsuzuki;Kazumi Tanaka;S. Kuwahara;T. Miyazawa
在我们最近对共轭二十碳五烯酸（CEPA）的抗肿瘤作用的研究过程中，我们发现通过在乙二醇中用KOH处理EPA制备的酸混合物通过膜磷脂过氧化诱导人肿瘤细胞的有效凋亡细胞死亡。有趣的是，KOH处理的CEPA混合物比EPA和CLA更具细胞毒性，对正常人成纤维细胞没有影响。为了确定CEPA混合物中的特定细胞毒性FA，我们合成了活性物质的可能候选物。本文报道了（5E，7E，9E，14Z，17Z）-5，7，9，14，17-二十碳五烯酸（E-CEPA）及其5-（Z）异构体（Z-CEPA）的合成。以5-氧代戊酸甲酯为起始原料，以3种Wittig反应为关键步骤，经6步反应合成了E-CEPA和Z-CEPA。接下来，我们检查了E-CEPA和Z-CEPA在人肿瘤细胞中的细胞毒性，并证实了它们的生物活性。E-CEPA和Z-CEPA对肿瘤细胞均有较强的细胞毒作用，且这种作用是通过诱导细胞凋亡来实现的。
During the course of our recent study on the antitumor effect of conjugated eicosapentaenoic acids (CEPA), we found that acid mixtures prepared by treating EPA with KOH in ethylene glycol induced potent apoptotic cell death in human tumor cells via membrane phospholipid peroxidation. Interestingly, the KOH-treated CEPA mixtures were more cytotoxic than EPA and CLA and had no effect on normal human fibroblast cells. To identify the specific cytotoxic FA in the CEPA mixture, we synthesized possible candidates for the active species. Here, we report the synthesis of (5E,7E,9E,14Z,17Z)-5,7,9,14,17-eicosapentaenoic acid (E-CEPA) and its 5-(Z) isomer (Z-CEPA), both of which are conjugated trienes that exist naturally in red algae (Ptilota filicina J. Agardh). E-CEPA and Z-CEPA were synthesized from methyl 5-oxopentanoate in six steps, using three types of Wittig reactions as the key steps. Next, we examined the cytotoxicity of E-CEPA and Z-CEPA in human tumor cells and confirmed their bioactivity. Both E-CEPA and Z-CEPA had a strong cytotoxic reaction in tumor cells, and this effect occurred through induction of apoptosis.
影响因子：
4.7
作者：
HA, YL;GRIMM, NK;PARIZA, MW
通讯作者：
PARIZA, MW
影响因子：
4.7
作者：
Ji, C;Rouzer, CA;Pietenpol, JA
通讯作者：
Pietenpol, JA