Design, synthesis and anti-gastric carcinoma activity of 1-styryl isoquinoline derivatives

To explore novel and effective anti-gastric agents, 26 1-styryl isoquinoline derivatives were designed and synthesized by one-step reaction based on Resveratrol. Evaluation of antitumor activity via CCK-8 assay suggested that these compounds had significant anti-proliferation activities against gastric cancer cell lines, especially compounds 14 and 20 with IC 50 values of 0.04 mu M and 0.08 mu M against HGC-27 cell line respectively. Simultaneously, these compounds had low toxicity on normal cells (GES-1, WI-38). Further mechanism studies demonstrated that compounds 14 and 20 possibly induced cell apoptosis through the mitochondrial apoptotic pathway which was activated by inhibiting signaling pathway PI3K/Akt/mTOR. Besides, it was found that compounds 14 and 20 arrested cell cycle at G 2 /M phase and both of them had obvious anti-migration and anti-invasion potential. Therefore, this work may offer a promising strategy for developing anti-gastric lead compounds worthy of further investigatin.

Automated summary

This study designed and synthesized a series of 1-styryl isoquinoline derivatives, and demonstrated that compounds 14 and 20 had significant anti-proliferation activities against gastric cancer cells, with low toxicity on normal cells. Mechanism studies suggested that compounds 14 and 20 induced cell apoptosis through inhibiting the PI3K/Akt/mTOR signaling pathway and activating the mitochondrial apoptotic pathway. Additionally, compounds 14 and 20 showed anti-migration and anti-invasion potential.