Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy
Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy
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DOI：
10.1016/j.ejmech.2012.11.031
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发表时间：
2013-02-01
影响因子：
6.7
通讯作者：
Tezuka, Yasuhiro
中科院分区：
文献类型：
--
作者：
Kudou, Naoki;Taniguchi, Akira;Tezuka, Yasuhiro
合成了一系列具有不同修饰的 O-烷基的新型 (-)-牛蒡苷元衍生物，并在营养缺乏的条件下评估了它们对人胰腺癌细胞系 PANC-1 的优先细胞毒性。结果表明，单乙氧基衍生物4i（PC50，0.49μM）、二乙氧基衍生物4h（PC50，0.66μM）和三乙氧基衍生物4m（PC50，0.78μM）在营养剥夺条件下表现出优先的细胞毒性，其与（-）-牛蒡甙元（1）（PC50，0.78μM）相同或更有效。 0.80μM）。其中，我们选择了三乙氧基衍生物4m，并使用小鼠异种移植模型检查了其体内抗肿瘤活性。三乙氧基衍生物 4m 还表现出体内抗肿瘤活性，其效力与 (-)-牛蒡苷元 (1) 相同或略强。这些结果表明，(-)-牛蒡苷元结构的修饰可能会产生一种基于反紧缩策略的新药。 (C) 2012 Elsevier Masson SAS。版权所有。
A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC50, 0.49 mu M), diethoxy derivative 4h (PC50, 0.66 mu M), and triethoxy derivative 4m (PC50, 0.78. mu M) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC50, 0.80 mu M). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy. (C) 2012 Elsevier Masson SAS. All rights reserved.