School of Pharmacy, Lanzhou University, 199 Donggang West Road, Lanzhou 730020, China.
Int J Mol Sci. 2022 Jul 21;23(14):8028. doi: 10.3390/ijms23148028.
Isaindigotone is an alkaloid containing a pyrrolo-[]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC) of 1.45 μM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.
异吲哚酮是一种生物碱，含有吡咯并[ ]喹唑啉部分与亚苄基共轭，从 Fort 的根部分离得到。然而，这种生物碱及其衍生物的进一步抗癌活性尚未得到充分探索。在这项工作中，合成了一种新型异吲哚酮衍生物，并使用三种不同的胃细胞系和一种人上皮胃细胞系研究了新型异吲哚酮衍生物 BLG26 的抗增殖作用。HGC27 细胞和 AGS 细胞进一步探讨了潜在的机制。BLG26 在 AGS 细胞中表现出更好的抗增殖活性，其半最大抑制浓度（IC）为 1.45 μM。BLG26 通过抑制线粒体凋亡途径和 PI3K/AKT/mTOR 轴，导致 HGC27 细胞和 AGS 细胞的线粒体膜电位丧失和诱导细胞凋亡。急性毒性实验表明，BLG26 的 LD（半数致死剂量）大于 1000.0 mg/kg。这项研究表明，BLG26 可能是治疗胃癌的潜在候选药物。
