Synthesis And Bioactivity Of Ferulic Acid Derivatives Containing Sulfonamide Moiety

Sulfonamides have attracted widespread attention of pesticide scientists because of their wide biological activities such as bacteriostasis,anti-virus and insecticide.The natural product ferulic acid compounds have been widely researched and applied in the field of pesticides and medicine.The research group designed and synthesized a series of ferulic acid derivatives in the early stage,and tested their biological activity against plant viruses.The test results show that the ferulic acid derivatives designed and synthesized have excellent anti-tobacco mosaic virus?TMV?and cucumber mosaic virus?CMV?activities.On the basis of this work,sulfonamide compounds with broad biological activity were found.In order to increase the types of new antiviral agents,we adopted the principle of active splicing to introduce the sulfonamide structure into the ferulic acid structure,and designed and synthesized 20target compounds 1a–1t.These designed and synthesized target compounds were characterized by infrared spectroscopy?IR?,nuclear magnetic resonance hydrogen spectroscopy?¹H NMR?,nuclear magnetic resonance carbon spectroscopy(¹³C NMR),and high-resolution mass spectrometry?HRMS?,and the target compounds were tested for biological activity against tobacco mosaic virus.At the same time,the microthermal surge method and molecular docking were used to study the interaction between some target compounds and the tobacco mosaic virus coat protein.The work completed in this paper is as follows:1.Taking the synthesis of target compound 1g as an example,the synthesis conditions of target compounds were explored from reaction temperature,feed ratio,catalyst,solvent and reaction time.It was determined that the better reaction conditions were acetonitrile as the solvent,potassium carbonate as the catalyst,the feed ratio was Intermediate 1:Intermediate 2:Potassium carbonate=1:1.2:2,the reaction was carried out under the heating temperature of 78?,the reaction time 6-8h under reflux.2.The ferulic acid derivatives containing sulfonamide structure were tested for the biological activity of plant viruses against tobacco mosaic virus?TMV?using the half leaf method.The results of the test indicate that at the mass concentration of 500?g/m L of the test compound,the curative activity inhibition rate of the series of compounds against tobacco mosaic virus was 26.9%?57.9%,and the range of protective activity inhibition rate was 31.2%?59.7%.The range of passivation activity inhibition rate was 43.7?87.3%.Among them,the curative activities of compounds 1f,1g,11 and 1n against tobacco mosaic virus were 50.3%,57.9%,55.3%,and 50.6%,all exceeding the control agent ribavirin?49.3%?.The protective activities of compounds 1b,1g,1j,11m,1n,1n and 1p against tobacco mosaic virus were 59.7%,53.3%,49.8%,53.7%,53.7%,52.7%,55.9%,which were higher than the control agents ribavirin?48.6%?,of which the protective activity of 1b was higher than that of the control agent ningnanmycin?54.1%?.The passivation effects of compounds 1b,1g,1i,1j,and 1p on tobacco mosaic virus were 87.3%,77.7%,76.9%,74.1%,and 73.7%,which were higher than the control agent ribavirin?72.7%?.The passivation activity of 1b is comparable to the control agent ningnanmycin?88.3%?.The effective median concentration(EC₅₀)of compound 1b for the passivation of tobacco mosaic virus was84.8?g/m L,which was better than the control agent ribavirin?138.3?g/m L?.3.The morphological destruction of the most active compound 1b and tobacco mosaic virus was observed by transmission electron microscope.The results show that the target compound 1b can obviously destroy the complete morphology of the virus particles and cause irreversible effects.4.The binding affinity of compound 1b to the coat protein of tobacco mosaic virus was studied using a micro heat surge instrument.The results show that compound lb has a strong binding capacity to TMV-CP?K_d=12.6?M?,which is significantly better than ribavirin?K_d=223.0?M?.5.The binding site of compound 1b and TMV-CP was studied by using molecular docking software.The results show that compound lb can hydrogen bond with amino acids on the coat protein of tobacco mosaic virus molecules,and the number of hydrogen bonds is more than the number of hydrogen bonds between ribavirin and the coat protein of tobacco mosaic virus.