Synthesis And Preliminary Exploration Of Anti-hepatoma Mechanism Of Flavonoids

Liver cancer is one of the most common primary malignant tumors in China and so far as to the entire world.According to the investigation,for many years,the incidence and mortality of liver cancer have remained a high degree in the population,and the current diagnostic methods and treatment methods are limited,the prognosis and outcome of patients are poor,and the five-year survival rate is not good.Flavonoids have many pharmacological effects such as anti-tumor,antiviral,antibacterial,and activity,of which many advances have been made in anti-liver cancer.However,natural flavonoids still have many disadvantages,such as less active ingredient content and not very satisfactory effect.Therefore,according to the characteristics of anti-tumor pharmacological activity and low toxicity of natural flavonoids,a series of flavonoids were designed and synthesized freshly by the chemical synthesis method with the effects of proliferation inhibition and apoptosis induction of glucosamine HepG₂cells.These compounds were used as the next experimental subjects to explore the inhibitory effect and mechanism of proliferation of HepG2 cells preliminarily.First of all,flavonoids were synthesized from2,4-dihydroxyacetophenone and benzoyl chloride,p-fluorobenzoyl chloride,p-bromobenzoyl chloride,p-methylbenzoyl chloride,p-methoxybenzoyl chloride,p-nitrobenzoyl chloride,furoyl chloride,2-thienoyl chloride,2-naphthoyl chloride,and then combined with the amino group on the glucosamine to obtain 10 target compounds,which were named by Xhbb-a～Xhbb-j.All the compounds were characterized by nuclear magnetic resonance hydrogen,carbon spectroscopy and high-resolution mass spectrometry to determine the molecular structure.Then the effects of compounds on the proliferation of human hepatocellular carcinoma HepG2 cells cultured in vitro at different concentrations were detected by MTT colorimetric assay,and the experimental results presented that compounds Xhbb-a～Xhbb-j had a determinate inhibitory effect on cells proliferation.According to the appropriate concentration selected,the apoptosis of hepatoma HepG2 cells treated with the compounds was detected and analyzed by Annexin V-FITC/PI double staining on flow cytometer,and the experimental results indicated that there were a large number of cells in late apoptosis.These results indicated that compounds Xhbb-a～Xhbb-j inhibited the proliferation of HepG2 cells by inducing late apoptosis of hepatoma cells in a dose-dependent manner.The drug-likeness analysis indicated that most of the compounds are accord with Lipinski’s Rule of Five.This study demonstrated that the synthesized 10 flavonoids freshly have a determinate anti-proliferation inhibition and promote apoptosis effects against hepatocellular carcinoma cells,which is laying the foundation for a deeper study of the mechanism of action,and promising to broaden ideas for the development of novel drugs for the treatment of hepatocellular carcinoma.