Journal of Enzyme Inhibition and Medicinal Chemistry (Dec 2022)

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

  • Kangjia Du,
  • Wantong Ma,
  • Chengjie Yang,
  • Zhongkun Zhou,
  • Shujian Hu,
  • Yanan Tian,
  • Hao Zhang,
  • Yunhao Ma,
  • Xinrong Jiang,
  • Hongmei Zhu,
  • Huanxiang Liu,
  • Peng Chen,
  • Yingqian Liu

DOI
https://doi.org/10.1080/14756366.2022.2065672
Journal volume & issue
Vol. 37, no. 1
pp. 1212 – 1226

Abstract

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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.

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