1. Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents.
- Author
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Kangjia Du, Wantong Ma, Chengjie Yang, Zhongkun Zhou, Shujian Hu, Yanan Tian, Hao Zhang, Yunhao Ma, Xinrong Jiang, Hongmei Zhu, Huanxiang Liu, Peng Chen, and Yingqian Liu
- Subjects
MEMBRANE potential ,GASTROINTESTINAL cancer ,MITOCHONDRIAL membranes ,STOMACH cancer ,CELLULAR signal transduction ,CANCER cells - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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