Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents

Journal of Enzyme Inhibition and Medicinal Chemistry

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