Design, Synthesis And Biological Activity Of Myricetin Derivatives Containing Sulfonate And Pyrimidine Groups

Myricetin is a kind of natural flavonoids and polyphenols,which has a wide range of biological activities,such as,antibacterial,antiviral,anticancer and antioxidant;sulfonates are important intermediates in organic synthesis,and compounds containing aryl sulfonates have outstanding biological activities such as antiviral,antibacterial,insecticidal and anticancer;pyrimidines are a kind of heterocyclic compounds with antibacterial and antiviral activities Cyclic compounds are widely used in medicine and pesticides.In this paper,myricetin derivatives containing sulfonate(A₁-A₂₂)and pyrimidine(B₁-B₂₄)were designed and synthesized by introducing sulfonate and pyrimidine heterocycles into myricetin.The structures of all the target compounds were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS and the structure of compounds A₃,A₁₁,A₁₄ and B₇ were further confirmed by X-ray single crystal diffraction.Their antibacterial and antiviral activities were tested.The antibacterial activity of the target compound was tested by turbidimetric method.The test results showed at the concentration of 100μg/m L that the inhibition rates of compounds A₅,A₁₁,A₁₄,A₁₅,B₃ and B₈ against Xanthomonas axonopodis pv.citri（Xac）were 95.3,88.0,93.0,90.9,91.3 and 85.3%,respectively,which were better than those of the lead compound myricetin（47.6%）,commercial agents bismerthiazol（66.4%）and thiodiazole copper（56.9%）;the inhibition rates of compounds A₁,A₄,A₈,A₁₀,A₁₃,A₁₆,B₃,B₄,B₈,B₁₁ and B₁₅ against Ralstonia solanacearum（Rs）were 85.1、86.7、87.7、92.9、90.7、87.3、90.9、83.9、92.8、88.7、90.4%,respectively;which superior to those of the lead compounds myricetin（40.5%）,commercial agents bismerthiazol（50.4%）and thiodiazole copper（47.6%）;the inhibition rates of A₂、A₃、A₈、A₁₀、A₁₈、B₃、B₈、B₁₆ against Xanthomonas oryzae pv.Oryzae（Xoo）ranged from 80.0-94.6%,which were better than those of the lead compounds myricetin（40.5%）,commercial agents bismerthiazol（50.4）and thiodiazole copper（47.6%）.The control effect of compound A₁₀ and B₃ on rice bacterial blight in vivo was determined by leaf-cutting method in greenhouse.The results showed that the protective activity and curative activity of compound A₁₀ were 40.7%and 47.9%at the concentration of 200μg/m L,respectively,which were better than those of bismerthiazol（35.2%,39.7%）and thiodiazole copper（30.8%,27.3%）;The protective activity and curative activity of compound B₃against rice bacterial blight were 42.4%and 49.2%,respectively,which were better than those of the bismerthiazol（35.2%,39.1%）and thiodiazole copper（30.8%,27.3%）.The mechanism of action of target compounds A₁₀,B₃ against Xoo and A₅ against Xac were observed by scanning electron microscope.The results showed that the antibacterial mechanism of compounds A₁₀,B₃ against Xoo and A₅ against Xac be achieved by destroying the cell membrane structure of bacteria,resulting in the incomplete structure of bacteria.The results showed that B₂₀,B₂₃ and B₂₄ at the concentration of 500μg/m L had better curative effect against TMV with inhibition rates of 52.3,53.7 and 47.1%respectively,which were better than that of ningnanmycin（43.1%）.The target compounds B₆,B₇,B₁₇ and B₂₃ also had good protective activity against TMV,and the inhibition rates were 61.5,51.9,58.3 and 61.1%,which were better than ningnanmycin（54.0%）.