Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells

Yun Hao Ma, Wan Tong Ma, Zhong Kun Zhou, Xiu Huang, Xin Rong Jiang, Kang Jia Du, Meng Ze Sun, Hao Zhang, Hong Fang, Yi Zhao, Hong Mei Zhu, Huan Xiang Liu, Peng Chen, Ying Qian Liu

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)


Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Original languageEnglish
Pages (from-to)963-971
Number of pages9
JournalJournal of Natural Products
Issue number4
Publication statusPublished - 22 Apr 2022
Externally publishedYes


Dive into the research topics of 'Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells'. Together they form a unique fingerprint.

Cite this