Design, Synthesis And Biological Activity Of Myricetin Derivatives Containing Bishydrazide Or Isoxazol

Myricetin is a kind of natural flavonol compound,which has been widely concerned for its antibacterial,anti-inflammatory,anti-tumor,antiviral and hypoglycemic effects,as well as its antibacterial and anti-tobacco mosaic virus（TMV）biological activities in agriculture.In this study,myricetin was used as the lead compound,50 myricetin derivatives containing bishydrazide or isoxazole were designed and synthesized by introducing the active group bishydrazide and isoxazole to the 3-hydroxy group of myricetin,and all compounds were characterized by NMR and HRMS.The antibacterial,antifungal and anti-TMV biological activities of all synthesized compounds were evaluated.In addition,the insecticidal activity of myricetin derivatives containing bishydrazide was also evaluated.The results of bacteriostatic activity test showed that the inhibition rates of G5 and Y25 on Xoo were 67.0 and 68.2%at 100μg/mL,respectively,which were better those that of bismerthiazol（65.0%）.The synthesized compounds showed low inhibition rate against the three plant derived bacteria Xac,Xoo and Psa.The results of antifungal activity test showed that Y3 had obvious inhibitory effect on Ss,and the EC₅₀ value was 13.2μg/mL,was better than kresoxim-methy（46.4μg/mL）and azoxystrobin（23.0μg/mL）.The results showed that the rape sprayed with compound Y3 had better protective activity in vivo.At 200μg/mL,the control efficacy on isolated leaves was 69.2%,which was lower than that of commercial fungicide azoxystrobin（83.3%）.The results of cell content release and cell permeability test showed that the nucleic acid content and soluble protein release of Sclerotinia sclerotiorum after Y3 treatment were obvious.The relative conductivity was significantly higher than that of the control group,so it was speculated that Y3 could cause the destruction of the cell membrane of the mycelium,and then lead to the death of the mycelium.The anti-TMV activity test results showed that the EC₅₀ values of the curative activities of compounds G9,G12,G13,G17 and Y18 anti-TMV were 202.3,209.7,297.3,274.4 and 286.7μg/mL,respectively,better than ningnanmycin（329.1μg/mL）.The EC₅₀ values of the protective activities of compounds G9,G13,G14 and Y18 anti-TMV were 164.0,211.7,218.7 and 210.1μg/mL,respectively,better than ningnanmycin（230.3μg/mL）.The microscale thermophoresis test showed that the K_dvalues of compounds G9,G13,G17 and Y18 and TMV-CP were 0.158,0.201,0.925and 0.855μmol/L,respectively.It was far superior to myricetin（71.220μmol/L）and ningnanmycin（2.074μmol/L）.G9,G13,G17 and Y18 have strong binding affinity with TMV-CP.Molecular docking simulation showed that there were many interactions between G9 and Y18 and TMV-CP,and they interacted with many key amino acid residues.G9 and Y18 may hinder the self-assembly of TMV particles.Chlorophyll content and POD activity showed that after G9 treatment,the chlorophyll content and POD activity in tobacco leaves were relatively improved.The results showed that G9treatment could improve the photosynthetic capacity of tobacco leaves and the defense ability of tobacco leaves anti-TMV.The insecticidal activity showed that the mortality of G9 against mythimna separate was 95.2%at 200μg/mL,which was close to that of control agent tebufenozide（100%）.