Synthesis And Biological Activity Of Myricetin Derivatives Containing Thiazole Or Pyrazole Piperazine Amid

Myricetin is a flavonol compound extracted from the bark and leaves of Myricaceae plant Myrica rubra.It has a wide range of biological activities such as antiviral,antibacterial,antioxidant,anti-tumor and anti-inflammatory.Thiazole and pyrazole are important five-membered nitrogen-containing heterocyclic compounds with bactericidal and antiviral activities.In addition,most of the compounds containing the core part of the amide bond and the piperazine part also have good biological activity.They have been widely studied in the field of medicine and pesticides and have important research value.In this paper,based on the principle of active splicing,thiazole and amide bond splicing were introduced into myricetin,and pyrazole and piperazine were introduced into myricetin structure by amide bond splicing.Two kinds of amide-containing myricetin derivatives were designed and synthesized,and the structures of all target compounds were characterized by NMR and HRMS.The inhibitory effects of all compounds on plant pathogenic bacteria and fungi and the antiviral activity of some target compounds were tested.The inhibitory activities of all compounds against three plant pathogenic bacteria Xanthomonas axonopodis pv.citri.（Xac）,Pseudomonas syringae pv.actinidiae.（Psa）and Xanthomonas oryzae pv.oryzae.（Xoo）were tested.The results showed that D6had good biological activity against Xoo,and its EC₅₀value was 18.8μg/m L,which was higher than that of the control drugs thiodiazole copper(EC₅₀=52.9μg/m L)and bismerthiazol(EC₅₀=79.1μg/m L).The results of scanning electron microscopy showed that the cells without drug treatment had uniform size and complete morphology.The cells treated with drugs were shriveled and shrunk,the surface rupture was incomplete,and the morphology changed significantly.The inhibitory activities of the compounds against twelve plant pathogenic fungi were tested.The results showed that the EC₅₀value of D16 against Phytophthora capsici（Pc）was 11.3μg/m L,which was higher than that of azoxystrobin(EC₅₀=35.1μg/m L).The in vivo experiment of pepper leaves in vivo showed that compound D16could effectively inhibit Pc.The scanning electron microscope mechanism showed that the hyphae after drug treatment were all shrunk and folded,the branches were short and small,and the morphology changed.and the untreated hyphae had smooth surface,good growth and complete structure..In addition,D1 also had better antibacterial activity against Phomopsis（Ps）than the control drugs azoxystrobin(EC₅₀=50.7μg/m L)and fluopyram(EC₅₀=71.8μg/m L),and the EC₅₀value was 16.9μg/m L.The results of in vivo biological activity determination of D1 showed that when the concentration was 200μg/m L,the protective effect of kiwifruit treated with D1 was 74.9%,and the curative effect was 60.6%,which were higher than that of fluopyram（41.4 and 32.5%,respectively）,indicating that compound D1 had good antifungal activity against Ps in vivo.The biological activity evaluation results of D1on SDH showed that the compound had a certain inhibitory effect on SDH in the mycelia of Ps.In addition,the curative,protective and passivation effects of some target compounds on tobacco mosaic virus（TMV）were also tested.Ningnanmycin was used as the control drug.The results showed that A4 and A23 had certain antiviral activity.and the EC₅₀values of curative activity were 79.0 and 54.1μg/m L,respectively,which were higher than that of commercial drug ningnanmycin（157.4μg/m L）.The EC₅₀values of the protective activity were 103.3 and 91.2μg/m L,respectively,which were higher than that of ningnanmycin（126.0μg/m L）.The results of microscale thermophoresis（MST）showed that the K_dvalues of A4,A23,myricetin and ningnanmycin were 0.021±0.009 and 0.018±0.009μmol/L,respectively,which were higher than myricetin（45.060±19.574μmol/L）and ningnanmycin（2.840±0.960μmol/L）,indicating that A4 and A23 had stronger binding force with the TMV-CP than myricetin and ningnanmycin.The results showed that A series of compounds had certain inhibitory activity against viruses,and D series of compounds had certain inhibitory activity against bacteria and fungi,which could provide some reference for the study of green pesticides with natural products as lead compounds.