Synthesis And Biological Activity Of Myricetin Derivatives Containing Amides

In this paper,a series of myricetin derivatives containing 1,3,4-oxadiazoles amide?4a-4p?and ferulic acid amide?8a-8v?were synthesized and their antibacterial?Xac and Xoo?and antiviral?TMV?activities were evaluated.All target compounds were characterized by HRMS,¹H NMR and ¹³C NMR;Antibacterial activity of all target compounds were tested by turbidity method and bismerthiazol was used as the control.The results of bioassays demonstrated that the EC₅₀ values of compound 4a,4b,4d,4f,4j,8b,8d,8e,8f,8h,8i,8j,8m,8l,8n,8u and 8v against Xac were 18.5-59.1?g/mL,which were better than that of bismerthiazol?68.8?g/mL?;compounds 4c,4f,4j,8c and 8d also shows appreciable inhibitory effect against Xoo,with EC₅₀ values of 66.3?45.9?35.7?63.0 and 41.5?g/mL respectively,which were superior to that of bismerthiazol?69.3?g/mL?;The half-leaf method was used to test the antivirial activity of all target compounds and ningnanmycin being used as the control.Compounds 4a,4b and 4n showed significant curative activities against TMV,with EC₅₀ values of 362.6?385.0?and 272.8?g/mL respectively,which were better than ningnanmycin?428.8?g/mL?;meanwhile,compounds 4d,4e,4f,8l,8n and 8p demonstrated protective activities against TMV,with EC₅₀ valus of 404.0,406.0,235.6,196.1,425.3 and 386.7?g/mL respectively,which were superior to that of ningnanmycin?447.9?g/mL?;Microscale thermophoresis experiment showed that the K_d value beteen compounds 4f,8l and TMV CP were 0.2 and 0.3?mol/L,which were better than those of myricetin and ningnanmycin,it is means that compound 4f and 8l have strong interaction with TMV CP.