Synthesis,Biological Activity And Molecular Docking Of Acylthiourea Derivatives

With the increasing abuse of chemical pesticides,which leads to drug resistance of target plants,and a large number of pesticide compounds in the environment can not be decomposed,causing serious pollution.At the same time,it has great harm to human health and livingenvironment.Therefore,it is urgent to develop green,environmentally friendly,easily degradable and harmless pesticides.In this research,according to the pharmacophore binding strategy and principle of bioelectronic isobaric,use the sulfonylurea herbicide compound molecule as the parent structure,replace the sulfonyl group in the sulfonylurea bridge with a carbonyl group,and replace the oxygen atom with a sulfur atom to obtain an acylthiourea structure.Then introduce methyl sulfone group to replace benzene and substituted aniline in the structure of acyl thiourea,PEG-400 as a phase transfer catalyst,a series of novel thiourea compounds containing aniline were designed and synthesized.Generalchemicalname:N-（（2-fluoro-5-（trifluoromethyl）phenyl）carbamothioyl）-4-（methylsulfonyl）-2-nitrobenzamide（4a）;General structure:（?）The structure of the target compound was identified by element analysis,infrared spectroscopy,hydrogen nuclear magnetic resonance spectroscopy,carbon spectroscopy,mass spectrometry.Finally,we analyzed and summarized the general laws of the spectral characteristics of these compounds.The herbicidal activity of the target compound was determined.The preliminary herbicidal activity tests showed that all compounds showed different biological activities to rape,soybean and wheat.Compounds 4a,4d,4h,4j,4l and 4n showed more than 80%inhibition on rape roots at the concentration of 100 mg·L^-1.Most of the compounds promoted the growth of soybean stem,but all of them inhibited the growth of wheat at high concentration.Because the target compounds and sulfonylureas are isosteric,we chose rape as the target plant and tested the inhibitory ability of the target compounds on the activity of acetyllactate synthase（AHAs）in vivo.The results showed that compounds 4l（44.44%）,4j（32.22%）and 4f（31.03%）had strong inhibitory activity.Compounds 4a,4g,4h,4k,4m and 4q also had good inhibitory activity on AHAS.Therefore,we speculate that these compounds may inhibit the growth of tested plants by inhibiting the activity of AHAS.In order to further study the inhibition mechanism of target compounds on AHAS enzyme,the molecular docking simulation software was used to analyze the binding mode between target compounds and enzyme molecules,to clarify the possible herbicidal activity mechanism of these compounds.This study can provide some data and theoretical basis for the design and virtual screening of acylthioureas in the future.