Natural Drug Discovery Laboratory, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Bioorg Med Chem Lett. 2021 May 15;40:127967. doi: 10.1016/j.bmcl.2021.127967. Epub 2021 Mar 19.
An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC value of 0.7 μg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4'-O-methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4'-O-methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrient-rich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4'-O-methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.
从鱼藤属植物花的乙醇提取物在营养缺乏条件下对人胰腺癌细胞 PANC-1 显示出很强的选择性细胞毒性，PC 值为 0.7μg/mL。对这种活性提取物的植物化学研究导致分离出四种异戊烯基异黄酮（1-4），包括一种新化合物命名为 4'-O-甲基高圣黄酮（1）。新化合物的结构通过高分辨 FABMS 和 NMR 光谱分析得到阐明。分离出的化合物在营养缺乏条件下对四种不同的人胰腺癌细胞系表现出很强的抗饥饿活性。新化合物 4'-O-甲基高圣黄酮（1）也被发现能够抑制营养丰富条件下 PANC-1 细胞的迁移和集落形成。在机制上，化合物 1 抑制 Akt/mTOR 信号通路中的关键存活蛋白。因此，4'-O-甲基高圣黄酮（1）可以被认为是基于抗饥饿策略的抗癌药物开发的潜在先导化合物。
