Design, Synthesis and Biological Evaluation of Neocryptolepine Derivatives as Potential Anti-Gastric Cancer Agents

Yunhao Ma, Yanan Tian, Zhongkun Zhou, Shude Chen, Kangjia Du, Hao Zhang, Xinrong Jiang, Juan Lu, Yuqing Niu, Lixue Tu, Jie Wang, Huanxiang Liu, Hongmei Zhu, Peng Chen, Yingqian Liu

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.

原文English
文章編號11924
期刊International Journal of Molecular Sciences
23
發行號19
DOIs
出版狀態Published - 10月 2022
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