Design,Synthesis And Antifungal Activity Of Novel 3-arylisoquinoline (Salts) Derivatives

Plant pathogenic fungi always been a threat to food security and was one of the main factors causing crop yield and quality decline.In addition,some phytopathogenic fungi can produce variety of toxins and metabolites which harmful to human and livestock,posed a threat to the safety of agricultural products.At present,with the continuous use of chemical fungicides,pesticide residues,drug resistance,environmental pollution and other shortcomings gradually exposed.Therefore,it was urgent to develop new green fungicides to prevent and control crop fungal diseases,ensure food security and maintain healthy living environment.Due to the extensive biological properties and environment friendly,the natural product-based or-derived compounds have attracted considerable attention as potential candidates to develop novel agrochemicals.A variety of plant fungicides have been widely used in the control of agricultural diseases.In this work,we designed and synthesized two series of 3-aryl-substituted isoquinoline（salts）derivatives based on"common"bionic skeleton 3-arylisoquinoline of Sanguinarine,Chelerythine and Berbrine.Their structure was identified by ¹H-NMR,¹³C-NMR,¹H-¹H COSY and HRMS.Preliminary,in vitro antifungal activity was tested by mycelium growth rate method.The result showed that most of the compounds had moderate to significant inhibitory activity against the five-tested plant pathogens（Alternaria solani,Fusahum graminearum,Alternaria alternata,Fusarium oxysporum and Physalospora piricola）,and some compounds exhibited equal antifungal activity to positive controls（Chlorothalonil and Carbendazim）.The EC₅₀ of 9f was 3.651mg·L^-1,which was close to chlorothalonil(EC₅₀=3.869 mg·L^-1).Further in vivo antifungal activity of compound 9f was studied on apples at the concentration of 50 mg·L^-1 and 100mg·L^-1,the protective and therapeutic activities against P.piricola were 64.957-80.342%and70.455-81.667%,respectively,which were near to chlorothalonil（73.078～76.923%and80.303～86.667%）.Structure-activity relationships showed that when the 3-aryl was benzene ring,the antifungal activity of 3’-substitued（8p-8s,9p-9s）was much lower than that of 4’-substitued（8b-8e,9b-9e）.Finally,molecular electrostatic potential analysis and molecular docking analysis revealed that 9f was fully covered by positive potential contour and easier to interactive with the reside groups of target protein than 8f.There was significant differences in the modes of action between 8f and 9f with the receptor,stated the different antifungal activity between 8 and 9.In conclusion,this paper provides experimental basis for the development of plant-derived antifungal agents.