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Design, synthesis, and biological evaluation of 3′,4′,5′‐trimethoxy evodiamine derivatives as potential antitumor agents

A series of compounds bearing 3′,4′,5′‐trimethoxy module into the core structure of evodiamine were designed and synthesized. The synthesized compounds were screened in vitro for their antitumor potential. MTT results showed that compounds 14a–14c and 14i–14j had significant effects, with compound 14h being the most prominent, with an IC50 value of 3.3 ± 1.5 μM, which was lower than evodiamine and 5‐Fu. Subsequent experiments further confirmed that compound 14h could inhibit cell proliferation and migration, and induce G2/M phase arrest to inhibit the proliferation of HGC‐27 cells, which is consistent with the results of the cytotoxicity experiment. Besides, 14h could inhibit microtubule assembly and might kill tumor cells by inhibiting VEGF and glycolysis. All experimental results indicate that compound 14h might be a potential drug candidate for the treatment of gastric cancer and was worthy of further study.