Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents. (31st December 2022)

• Record Type: Journal Article
• Authors: Du, Kangjia; Ma, Wantong; Yang, Chengjie; Zhou, Zhongkun; Hu, Shujian; Tian, Yanan; Zhang, Hao; Ma, Yunhao; Jiang, Xinrong; Zhu, Hongmei; Liu, Huanxiang; Chen, Peng; Liu, Yingqian
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1212
• Page End: 1226
• Publication Date: 2022-12-31
• Subjects: Isaindigotone -- cytotoxicity -- MMP -- apoptosis -- PI3K/AKT/mTOR; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2065672
• Languages: English
• ISSNs: 1475-6366

Abstract

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. Graphical Abstract: UF0001