Synthesis And Anti-tumor Activity Of Tryptamine Salicylic Acid Derivatives

Objective Melatonin has a wide range of antitumor activity,it has the effect of down-regulating HIF-1,which can down-regulate key enzymes in glycolysis,such as HK and PFK.At present,there are many research focusing on mechanisms for the anti-tumor effect of aspirin.Since aspirin can reduce the level of glycolysis in tumor tissues by down-regulating PFK,we designed to replace the acetyl group on melatonin with aspirin,synthesizing Tryptamine salicylic acid derivatives which has the effect of inhibiting tumor glycolysis.Methods The anilines of different substituents were used as raw materials to synthesize benzoquinone hydrochloride by sodium nitrite method,and then substituted by different cyclidine derivatives,then compounded with different substituents by amide bond.Their structure were characterized by ¹H NMR,¹²C NMR and MS.The target compound was detected by MTT assaying on anti-proliferative activity of human breast cancer cell line?MCF-7?,human lung cancer cell line?A549?,human hepatoma cell line?HepG2?,human gastric cancer cell line?MGC-803?and human cervical cancer cell line?Hela?.The colony forming ability and cell migration ability of compound E20 against MGC-803 cells were examined by cell colony assay and scratch assay.Flow cytometry was used to detect the effect of compound on the apoptosis and cycle of MGC-803 cells by flow cytometry.The effect of compound E20 on the expression of HIF-1?and glycolytic associated proteins HK-2 and PFK was examined by western blotting.Results 36 new tryptamine salicylic acid derivatives were synthesized and identified.Most of the tryptamine salicylic acid derivatives have anti-proliferative activity,and the compound E20exhibits the best anti-proliferative activity against human gastric cancer cells MGC-803,and can inhibit the colony forming ability and migration ability of MGC-803 cells.What's more compound E20 induces apoptosis of MGC-803 cells and arrest of the cell cycle in the G2/M phase.Compound E20 down-regulates the expression of the glycolytic associated protein HK-2.Conclusion The tryptaminesalicylic acid derivative N-[2-?5-bromo-1H-indol-3-yl?-ethyl]-2-hydroxy-3-methyl-benzamide ?E20?is potential anti-tumor drug candidates.The anti-tumor activity and its mechanism still need further study.