Preparation Of Glycosyl Benzimidazole And Isoxazole Derivatives And Their Antitumor Activities

More and more attention has been paid to the activity of the modified activated heterocyclic molecules due to their higher biological activity,improved water solubility and less toxic side effects.In recent years,a variety of glycosides with good biological activity have been emerging.Therefore,in order to enrich the glucoside compound library,it is of great significance to design and synthesize novel heterocyclic compounds which modified by sugar with potential biological activity.In this thesis,a series of novel glycosyl heterocyclic compounds were designed and synthesized with glucose,galactose and Arabia sugar as the source of sugar.On the basis of this,a total of 35 new compounds were synthesized,and their antitumor activities were studied.1.Design and synthesis glycosyl aldehyde oxime of different sugar groups,and the structure of these new compounds were characterized by ¹H NMR,¹³C NMR,HRMS and other methods.2.By using the method of active unit splicing and 1,3-dipolar cycloaddition,we synthesized a series of derivatives of the glycosyl benzimidazole derivatives and glycosyl benzimidazole derivatives.The structures of these new compounds were all charaterized by ¹H NMR,¹³C NMR and HRMS.3.Peracetylated glycosyl benzimidazole compounds 6a₁-6a₃/6b₁-6b₃/6c₁-6c₃for hepatocellular carcinoma were tested by MTT method?HepG₂ cells?and lung cancer?A549 cells?cell toxicity,and the results displayed that the antitumor activity of benzimidazoles glycosylation were improved,some of them have shown good anti-cancer activity.The abnormal activity of compound 6a₂/6b₂/6c₂ on A549 cells was preliminarily explained by the antitumor activity test of 7a₂,which was obtained by deprotection.In addition,we simulated the process of cell migration in vitro,and studied the effects of 6a₁-6a₃/6b₁-6b₃/6c₁-6c₃ and 7a₁-7a₃/7b₁-7b₃/7c₁-7c₃ on migration of HepG₂ cells and A549 cells by scratch assay.In summary,a series of heterocyclic compounds based on the precursor of new glycosylation of glucose,galactose and Arabia sugar were synthesized in this paper,and then 35 novel glycosyl benzimidazole and isoxazole compounds were achieved,the preliminary study on its antitumor activity,lays a foundation for the further study of the biological activity of these glycosyl benzimidazole compounds.