Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells
Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells
复制标题
4-氨基-4-脱羟基缩乳糖素衍生物的合成及其在葡萄糖饥饿的 A549 肿瘤细胞中的细胞毒性评价
DOI：
10.1016/j.bmcl.2014.12.061
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发表时间：
2015
影响因子：
2.7
通讯作者：
Lihong Hu
中科院分区：
文献类型：
--
作者：
Min Lei;Xianwen Gan;Kun Zhao;Qiang Yu;Lihong Hu
天然产物牛蒡甙元（ATG）在葡萄糖饥饿下表现出对癌细胞的优先细胞毒性。以先导化合物ATG为基础，通过生物电子等排修饰设计并合成了一系列4-氨基-4-脱羟基龙胆素衍生物。在葡萄糖饥饿的A549肿瘤细胞中评估它们的细胞毒性，结果表明4-氨基-4-脱羟基缩牛蒡苷元比牛蒡苷元表现出更强的细胞毒性，并且4-氨基上的进一步取代基将导致细胞毒性显着降低。 4-取代的牛蒡苷元可以选择性地靶向葡萄糖饥饿的 A549 肿瘤细胞，这为抗癌药物开发提供了一种替代策略，且对正常组织的毒性最小。
The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity.