Journal of Enzyme Inhibition and Medicinal Chemistry | |
Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents | |
Xinrong Jiang1  Hao Zhang1  Wantong Ma1  Chengjie Yang1  Yunhao Ma1  Shujian Hu1  Peng Chen1  Hongmei Zhu1  Kangjia Du1  Huanxiang Liu1  Yingqian Liu1  Zhongkun Zhou1  Yanan Tian1  | |
[1] School of Pharmacy, Lanzhou University, Lanzhou, China; | |
关键词: Isaindigotone; cytotoxicity; MMP; apoptosis; PI3K/AKT/mTOR; | |
DOI : 10.1080/14756366.2022.2065672 | |
来源: DOAJ |
【 摘 要 】
A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1–26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 μM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.
【 授权许可】
Unknown