Antifungal Activities And Structure-Activity Relationship Of 2-aryl-7-chlorine-3,4-dihydroisoquinoline Salt Compounds

Plant pathogenic fungi have always been considered one of the major factors leading to plant diseases,which not only lead to the decline in the quality and quantity of agricultural products,but also a serious threat to human and animal health.For a long time,pesticides have become the main means of controlling phytopathogenic fungi,but the long-term use of pesticides has led to serious drug resistance and environmental problems.Therefore,the development of efficient,low toxicity and environmental friendly of plant-derived pesticides has become increasingly important.Natural isoquinolinium salts are an important component of isoquinoline alkaloids,and these compounds have become the focus of attention of researchers because of their special structure and extensive physiological activity.However,the low content,lively chemical properties,difficult to modify and other factors seriously restricted the drug development of such compounds.In the early stage of our study group,a series of analogues of isoquinolinium salts were designed and synthesized by using chelerythrine and sanguinarine as template compounds.The results of activity showed that these compounds had good antibacterial and acaricidal activity.They have potential application value.Based on the preliminary work of the laboratory,the activity of 2-aryl-7-chlorine-3,4-dihydroisoquinoline salt was tested for six plant pathogenic fungi and analysis the structure-activity relationship.The main results are as follows.1.Based on the mycelial growth rate method,The antifungal activities in vitro of the target compounds against six common plant pathogenic fungi was tested at 50?g/mL.Thiabendazole?TBZ?was used as a positive control.Sanguinarine?SA?was used as reference control.The results were shown as follows.All compounds presented inhibition activity and the activity of some compounds was higher than that of sanguinarine.For Alternaria alternate and Curvularia lunata,the inhibitory activity of most of the compounds is much higher than thiabendazole.thiabendazole showed high inhibitory activity for againsting Colletotrichum gloeosporioides,Fusarium solani,Fusarium oxysporium f.sp.Niveum and Valsa mali.But the inhibitory activity of some compounds was still higher than that of thiabendazole.The sensitivity of each plant pathogenic fungus to these compounds from high to low as follow,Colletotrichum gloeosporioides,Fusarium solani,Curvularia lunata,Alternaria alternate,Valsa mali,Fusarium oxysporium f.sp.Niveum.2.The compounds with higher initial activities were further subjected to median effective concentrations(EC₅₀)assay.The results showed that broad-spectrum antifungal activities was2.5-31.8?g/mL.These compounds showed high inhibitory activity to Fusarium solani.Seven compounds'EC₅₀ less than 10?g/mL,of which four were less than 5?g/mL.Compound A33showed the highest activity against Colletotrichum gloeosporioides,Fusarium oxysporium f.sp.Niveum and Valsa mali with EC₅₀ of 7.4,7.7,2.5?g/mL,respectively.Compound A25 showed the highest activity against Fusarium solani with EC₅₀ of 2.8?g/mL.Compound A4 showed the highest activity against Alternaria alternate and Curvularia lunata with EC₅₀0 of 5.5,7.8?g/mL,respectively.3.The structure-activity relationship indicates that A-ring and C-ring substituents affect the antibacterial activity of the compounds.The F-substituted compound exhibited a weak enhancement effect compared to the C-ring unsubstituted?H?,and the activity of the remaining substituents were reduced in varying degrees.The weakening effect of OH and NO₂substitution is most obvious.the contribution of the positions of substituents to the antibacterial activity of the compounds is that o>p>m except NO_2.In summary,this study evaluated the inhibitory activity of2-aryl-7-chlorine-3,4-dihydroisoquinoline salt on six plant pathogenic fungi,and analyzed the structure-activity relationship.The results showed that these compounds have good antibacterial activity,and some highly active compounds had great potential to develop new antimicrobial agents.At the same time,the study also provided reference for the subsequent structural optimization of the compounds and the design and synthesis of new drugs.It is necessary to further study on mechanism and bioactivity in vivo.