The Reserch On Antifungal Activity Of Three Kinds Of Isoquinoline Quaternary Ammonium Salt

Isoquinoline quaternary ammonium salt,which is a less part in isoquinoline alkaloid,but because of its active center C=N ?,a variety of physiological activity,such as antifungal,anticancer,antivirus and so on,is becoming a hot spot of new drug research.We have designed and synthesized A,B,Cthree categories N-ary 1-3,4-dihydro isoquinoline compounds,which is based on the natural activity of benzophen anthridine alkaloid compounds.All these compounds contain C=N+ active center.The 13 kinds of plant pathogenic frungal was used for test material,and the three kinds of synthetic N-aryl-3,4-dihydro isoquinoline was used for quasi fungus drug,mycelium growth rate method was used to study the antifungal activity and structure-activity relationship.Ultimately,the result provid theoretical guidance for structural optimization,development of antimicrobial drugs.The specific content of this reserch is as follows:1.Under the concentration of 50 ug/mL,this research studied the in vitro antifungal activity of three kinds of isoquinoline quaternary ammonium salt(A?B?C)to 13 kinds of plant pathogenic fungi,which adopt the mycelium growth rate method.Probenazole(TBZ)is used as positive control.The results showed that:when the concentration of 50 ug/mL,almost all compounds showed different degrees inhibition to 13 kinds of plant pathogenic fungal.Three kinds of compounds showed stronger inhibition to five kinds of pathogenic fungal-Alternaria alternate.Alternario solani?Alternaria.Curvularia lunata?Blast Fungus than the positive control TBZ.A parent compound shows the weakest antifungal activity,C parent compound shows the strongest antifungal activity,and has broad spectrum antimicrobial properties.Electron-withdrawing groups is introduced in the three groups of N-aromatic ring,the hydroxyl depress the activity of the parent compound,and the introduction of halogen?nitro can improve the activity of the parent compound.Introduction of electronic group methyl can significantly enhance parent compound activity,but the introduction of methoxyl group showed no effect on the parent compound.When reduced the concentration to 30 ug/mL,three kinds of compound N-aryl,2'-methyl substituted showed the strongest active,but the antifungal activity of other compounds decreased significantly.2.We Selected three types broad-spectrum and efficient antifungil compounds of the three kinds of compounds:A27,B14 and C33.We used this to test in vitro antifungil virulence.The results showed that the EC50 value of three kinds of compound are below 15 ug/mL.The EC50 values of A27 to Fusarium solani,Fusarium graminearum,Curvularia lunata is as follows:1.13 ug/mL,2.0 ug/mL,2.90 ug/mL.Comprehensive activity showed that antifungal activity of A27 to Fusarium solani,Fusarium graminearum,Curvularia lunata is the best.YWhen the substitution of methyl on 2'Tbit of three kinds of compud A27 showed the strongest activity,B14 was the weakest.3.The study of structure-activity relationship showed that the activity of three kinds of selected compounds is influenced by the position.the number and the variety of the substituent-After the introduction of substituents in compound A's N-taromatic,the antifungal activity was significantly enhanced,and has broad antifungal spectrum.After the introduction of substituents,B and C compounds showed no obvious increased antifungal activity.When 2'-methyl,2' and 4' halogen,3'nitro,2',6'-diF was respectively introduced in the N-aromatic ring,the activity of the parent compound can be enhanced.When F,Cl was introduced in the N-aromatic ring,The activity of it was stronger than Br,I was introduced in the N-aromatic ring.Position effect showed that the antifungal activity of halogen in the 2'and 4' bit stronger than that on the 3' bit.When hydroxyl in 2'Tand 4',the antifungal activity was stronger than it in the 3'.The introduction of nitro made individual compounds stronger than the parent compound,Position effect showed that:3'>4' bit>2' bit.The activity of Methoxy at different site showed 2'bit>3'bit>4'bit.The effects of methyl on three kinds of compounds are the most obvious,All of that showed inhibitory activity and was stronger than the parent compound.Methyl in 2' is stronger than in 4' and is stronger than in 3'.Methyl is the synergistic group.