Synthesis,Biological Activity And Molecular Docking Study Of Substituted Aniline Thiourea Derivatives

Food crisis is a common problem faced by people all over the world,which restricts social development and human progress.The development of new pesticides will effectively alleviate this crisis and solve the problem of food security and production.In this study,according to the bioisosteric and structure-activity relationship of urea compounds,the active substructures were spliced,the methylsulfone group-containing benzene ring and aniline derivatives were introduced into the thiourea structure,and two series of 24 kinds of thiourea derivatives were designed.The general structure is as follows:Series(I):N-(2-chloro-4-methylsulfonylbenzoyl)-N’-(substituted phenyl)thiourea Series(Ⅱ):N-(4-methylsulfonylbenzoyl)-N’-(substituted phenyl)thioureaIn this paper,24 title compounds were successfully synthesized from 4-methylsulfonyl benzoic acid and 2-chloro-4-methylsulfonyl benzoic acid by acylation reaction,isothiocyanate esterification reaction and nucleophilic addition reaction.In order to reduce environmental pollution,we adopt the green synthesis method called phase transfer catalysis,using polyethylene glyco1400 as the phase transfer catalyst to complete the isothiocyanate esterification reaction.After that,all the compounds were characterized by melting point,mass spectrometry,elemental analysis,infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy,which confirmed that the structures of all compounds were in line with expectations.Furthermore,the physicochemical properties,spectral properties and reaction methods of the targetcompounds were discussed in detail.In this study,the preliminary herbicidal activity determination method(Petri dish method)stipulated in the national new pesticide development and development was used to determine the preliminary herbicidal activity of two series of thioureaderivatives.The compounds showed different biological activities on three target crops:rape,soybean and wheat,and 13 thiourea compounds had a significant inhibitory effect on the roots of rape seeds at a concentration of 100mg/L.Compound Id had a relatively strong inhibitory effect on wheat roots at a concentration of 100 mg/L,and compound Ik had a certain inhibitory effect on wheat stems at a concentration of 100 mg/L.Because the target compounds had good inhibitory activity against rape,we selected rape as the target plant to complete the experiment of acetohydroxy acid synthase(AHAS)inhibition activity.Among all thiourea derivatives,compounds Ⅰp(86.95%),Ⅱg(87.70%)and Ⅱh(89.12%)showed excellent AHAS enzyme inhibitory activity.All the other compounds showed different levels of inhibitory activity,but relatively poor.Finally,the binding mode of thiourea derivatives with AHAS enzyme was studied by molecular docking simulation experiment.Based on the binding score,it was found that compounds Ⅰp and Ⅱh had the best binding mode with AHAS enzyme,and formed a large number of hydrogen bonds with different amino acid residues.Their lowest energy conformations occupiedless space than other compounds,they were easier to enter the binding pocketand bound to the amino acid residues.According to the results of herbicidal activity experiment,enzyme activity experiment and molecular docking experiment,it was known that in the design of this type of thiourea compounds,the nitro group should be introduced on the benzene ring of the aniline,which can significantly improve the biological activity of the thiourea compounds.