Design,Synthesis, And Structure?Activity Relationship Of 6-benzylamino-β-carbolines Derivatives As Antifungal Agents

β-carboline alkaloids are a kind of heterocyclic compound containing a common tricyclic pyrido[3,4-b]indole ring structure,which is widely existed on the earth and was originally isolated from Peganum harmala.Theβ-carboline alkaloids were extensively presented in extracts from plants,animals,and marine organism.Numerous studies have shown thatβ-carboline has a wide range of beneficial pharmacologic properties,including highly effective antifungal activity,and has the potential to be a candidate drug for botanical pesticides.These encouraging results can be providing an alternative,promising use of6-substitutedβ-carbolines through the design and exploration of eco-friendly fungicides with high efficiency.All compounds were evaluated for their antifungal activity in vitro.The results were summarized as follows:Theβ-carboline framework was prepared by three-step reactions containing the Pictet–Spengler reaction of L-tryptophan.After introducing a nitro group on the 6-position ofβ-carboline,the amino group was benzylated by the reductive amination of benzaldehyde.A series of derivatives were synthesized by the reaction of 6-amino-β-carboline with the corresponding aldehyde.The structure of all compounds was characterized by ¹H-NMR、¹³C-NMR、HR-MS.6-amino-β-carboline derivatives were evaluated for their antifungal activity in vitro using mycelium growth rate method.The most active compounds were tested for concentration for 50%of maximal effect(EC₅₀).Compounds V6a and V6h exhibited good antibacterial activities against Alternaria alternate,Alternaria solani,Pyricularia grisea and Mycosphaerella melonis,with inhibition rates of 62%–93%at a concentration of 150μM.Compounds V6a and V6h showed the best inhibitory activity against all the tested fungi,with concentration for 50%of maximal effect(EC₅₀)between 77 and 124μM.In this study,the structure-activity relationship of the antifungal activity of6-amino-β-carboline derivatives was preliminarily summarized:1)The substitution of amino group on the 6-position improves the activity on most of the fungi;2)The different substituents on the phenyl ring of the 6-amino-β-carboline derivatives had a significant effect on its antifungal activity.The effect of substituent position on the activity generally varies with the type of substituent and species of fungus.The presence of the methoxy group increases the activity against certain pathogenic fungi,but in some cases,it reduces the antibacterial activity against certain bacteria.The presence of 4-CF₃（V6h）increased the activity against in most cases.For the derivatization of the schiff base at 6-position of theβ-carboline,it was found that the change of the substituents on the aryl had little difference on antifungal activity,except that the presence of 3,4-Cl₂（V5j）increases the activity.In this study,β-carbolines were modified to obtain a number of compounds with excellent antifungal activity,which enriched the database of antifungal drugs and provided a theoretical basis for the development of antifungal drugs.