Design And Synthesis Of Sulfonamide-substituted Purine Nucleoside Derivatives And Research On Their Anti-plant Virus Activity And Mechanism Of Action

In this thesis,a wide range of bioactive sulfonamide structural units were introduced with purine nucleosides as the parent structure.A series of sulfonamide-substituted purine nucleoside derivatives 1-25 were designed and synthesized by ¹H NMR,¹³C NMR and HRMS.The cucumber mosaic virus and tobacco mosaic virus potato virus Y were used as research objects,and the target compounds were tested for live anti-plant virus activity by half-leaf method.Based on the anti-TMV inactivation activity of target compounds,the interaction between them and TMV CP was preliminarily investigated.Proteomics-related studies were carried out on target compound 5 based on the protective activity against CMV.The work summary of this paper is summarized as follows:1.The sulfonamide structure with broad biological activity was introduced into the purine nucleoside structure by the principle of active structure splicing.The 25 new sulfonamide-substituted purine nucleoside derivatives 1-25 were designed and synthesized.All compounds were characterized by ¹H NMR,¹³C NMR,HRMS and elemental structures.2.Using Ningnanmycin,ribavirin and amino oligosaccharides as control agents,the target compounds were tested for Cucumber Mosaic Virus?CMV?Potato Virus Y?PVY?and Tobacco Mosaic Virus?TMV?using the half-leaf spot method.At a concentration of 500?g/mL,most compounds have good inhibitory activity against PVY,CMV and TMV.Therefore,the EC₅₀ value of the target compound against CMV protective activity was further tested,among which compound 5(EC₅₀=237.55?g/mL),compound 1(EC₅₀=363.79?g/mL)and compound 2(EC₅₀=383.02?g/mL)were more effective than ninnamycin(EC₅₀=511.82?g/mL),ribavirin(EC₅₀=584.53?g/mL)and Chitosan oligosaccharide(EC₅₀=550.80?g/mL).In terms of anti-TMV activity,compound 4(EC₅₀=67.30?g/mL)and 5(EC₅₀=48.85?g/mL)showed better inactivation activity,respectively,than ningnanmycin(EC₅₀=84.78?g/mL)ribavirin(EC₅₀=150.45?g/mL)and aminooligosaccharide(EC₅₀=521.30?g/mL).3.Fluorescence spectroscopy was used to further explore the interaction between some target compounds and TMV CP.The results showed that the high activity compound 5 and TMV CP have strong affinity.4.The effect of compound 5 with better CMV protection activity on the biological activities of phenylalanine ammonia-lyase?PAL?superoxide dismutase?SOD?and peroxidase?POD?in leaves of plants was determined.Enhance defense enzyme activity to enhance tobacco disease resistance;use mass spectrometry to analyze differential protein expression between different conditions,and use various bioinformatics methods to annotate,classify and functionally analyze differentially expressed proteins to find compound regulation plant physiological and biochemical photosynthesis key pathways.