Synthesis of peiminine derivatives and its effect on A549 lung cancer‐bearing mice

Abstract To seek an effective anti‐lung cancer drug, a total of 14 derivatives were synthesized and characterized. The anti‐lung cancer effect of peiminine derivatives were evaluated in vitro and in vivo. The results of MTT and cell apoptosis assays showed that in comparison with peiminine and its other derivatives, compound 1c (indole‐3‐acetic acid‐peiminine ester) exhibited the highest activity with an IC 50 value of 12.78 ± 0.64 μM. Compound 1c (10 μM) significantly reduced the levels of IL‐6, TNF‐α, and IL‐1β in A549 cells. In addition, the qRT‐PCR results showed that compound 1c (10 μM) reduced the mRNA levels of TNF‐α, mTOR, Bcl‐2, Akt1, PI3K, and p65 and increased those of Bax and caspase‐9. Next, the anti‐lung cancer activity of compound 1c (5 mg/kg) was evaluated in A549‐bearing nude mice. It was revealed that the tumor size and weight were significantly inhibited after treatment with compound 1c . And the levels of IL‐6, TNF‐α, and IL‐1β were decreased in mouse tumors. Finally, the latent mechanism of compound 1c was explored by western blot analysis. It was revealed that compound 1c could decrease the expressions of NF‐κB, Bcl‐2, PI3K, Akt, and mTOR and increase the expressions of Bax and caspase‐9 abundance. In conclusion, compound 1c exhibits an inhibitory effect on lung cancer, which was found to occur via inhibition of the PI3K/AKT/mTOR/NF‐κB signaling pathway, thus representing a potential new lead compound for application in lung cancer therapy.