Synthesis And Antimicrobial Activity Of Schiff Base Of 6–Methoxyl–β–Carboline Derivatives

Plant diseases are one of the important concerns to agricultural production and food safety all over the world.Phytopathogenic fungi could infect the plant tissue in the process of their growth,which result in the yield losses and the quality decrease of agricultural products.In order to solve this problem,our pharmacological industries have produced lots of antibiotics.However,we are still facing embarrassing situation,with the emergence and enhancement of antibiotic resistance.Moreover,the WHO have advocated traditional medicines as safe remedies for both microbial and non-microbial diseases over the years.β-carboline alkaloids are an important class of natural products,because of its anti-cancer,anti-virus,antibacterial and other extensive biological activity,in recent years it become a hot research highlights.We want to explore its antibacterial activity,so we started with 5-methoxytryptamine,getting a class of Schiff base derivatives of β-carboline.Its anti-bacterial and antifungal activity were tested,hoping to find candidate compounds for agricultural fungicides.6-methoxyl-β-carboline was synthesized from 5-Methoxytryptamine via the Pictet-Spengler reaction,catalytic hydrogen transfer reaction and hydrolysis reaction.Then thorough amination reaction,we can get 26 derivatives of 6-methoxyl-β-carboline.And the structure of all compounds was identified by 1H-NMR,13C-NMR and ESI-MS,respectively,and its physical data were tested accurately.Using filter paper method,all the compounds were tested on antimicrobial activity in vitro againsit the eight pathogenetic bacteria with Penicillin Sodium and Fosfomycin Sodium as positive control.Antimicrobial activity test indicated that Bacillus subtills,Ralstonia solanacearum,Pseudomonas syringae pv.actinidiae,and Bacillus cereus,show good activity,and Pseudomonas solanacearum has the moderate activity,while compounds had no inhibitory activity against Escherichia coli,Staphylococcus aureus and Pseudomonas aeruginosa generally.Three compounds(5k,5l and 6e)had the equal activity to positive control,but no one was better than that of the positive control.The in vitro antifungal properties of all synthesized compounds were evaluated against four phytopathogenic fungi(Valsa mali,Fusarium coeruleum,Colletotrichum gloeosporioides and Mycosphaerella melonis)using the mycelium linear growth rate method.At a concentration of 50 μg/mL,Compounds 6j and 6k had the highest activity against M.melonis,with inhibition rates more than 80%,equal to that of Thiabendazole.Through analyzing the chemical structure and antibacterial activity of derivatives,1)The data showed that electron withdrawing groups have much higher antibacterial activity than electron donating group;2)When the parent skeleton was modified by the substituents including halogen,the iodine showed better antibacterial activities;3)When the parent skeleton was modified by the same substituents,ortho-substitution show the better activity.Generally;4)The length of the alkyl chain chain connecting C = N and the benzene had an effect on its antibacterial activity,but no definite conclusion has been obtained;5)The MICs of compounds 5k and 5l was 15.63 μg/mL against Pseudomonas syringae pv.actinidiae and compound 6e had 15.63 μg/mL against Ralstonia solanacearum;6)Interestingly,all of the tested compounds displayed better selectivity for the Gram-negative bacteria.The inhibition rates of most derivatives were higher than that of compound 4,which suggests that the C=N bond play an important role in antifungal activity.Twelve compounds of the tested compounds displayed more than 50% inhibition activity against Valsa mali;five compounds present 50% inhibition activity against Fusarium solan and eight compounds display 50% inhibition activity against Mycosphaerella melonis,which is better than compound 4.While these compounds have low inhibition activity against Colletotrichum gloeosporioides.Excitingly,the inhibition rates activity against Mycosphaerella melonis of 6k and 6l were more than 80%.In addition,we also could find out that derivatives with electron withdrawing groups have a better inhibitory activity.Some of these compounds(5k,6j and 6e)had very potent inhibitory activity against antibacterial,which were expected to become a new class of agricultural fungicide.