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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1212-1226
Number of pages15
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume37
Issue number1
DOIs
Publication statusPublished - 2022
Externally publishedYes

Keywords

  • Isaindigotone
  • MMP
  • PI3K/AKT/mTOR
  • apoptosis
  • cytotoxicity

Fingerprint

Dive into the research topics of 'Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents'. Together they form a unique fingerprint.

Cite this