Design,synthesis And Antimicrobial Activity Evaluation Of Polyamine Chemical Entities

Plant diseases pose a serious threat to global food security,resulting in reduced food production or the quality of agricultural products.According to statistics,plant diseases cause direct economic losses of hundreds of billions of dollars every year,bringing serious economic losses and social problems.One of the main ways to deal with this crisis is to develop new fungicides with high efficiency,low toxicity,environmental friendliness and unique action mechanism.Based on this,this paper starts with the construction of an"economic"antibacterial new chemical entity,constructs a variety of amine bactericidal chemical entity by using economic amine and aldehyde as raw materials,and then discusses its structure-activity relationship,defines its antibacterial mechanism,and provides a basis for the further development and utilization of amine compounds as an excellent antibacterial lead model,the creation of a new bactericidal agent with independent intellectual property rights.The main research contents are described as follows:1.Design,synthesis and evaluation of antibacterial activity of saturated aldehydes and diamine condensation derivativesBased on the previous research of our group,we continued to use 1,2-cyclohexanediamine and 1,3-cyclohexanedimethylamine as the parent nucleus skeleton and further obtained two series of derivatives A and B by reductive amination reactions with saturated aromatic and aliphatic aldehydes.The antibacterial activities of the derivatives were evaluated against six phytopathogenic fungi,four rot fungi,four phytopathogenic bacteria,and four food-borne bacteria.The results showed that most saturated amines showed better in vitro antibacterial activity than positive controls against eight bacteria.The MIC values of compounds A7,A18 and A20 against most phytopathogenic bacteria were below 25μg/m L.In particular,compound A7 showed excellent antibacterial activities against Xanthomonas oryzae pv.oryzae with MIC values of 3.12μg/m L.In particular,the aminated derivatives A17 and A18,which were synthesized from lily aldehyde and cyclamen aldehyde,showed good bactericidal activity and broad spectrum.2.Design,synthesis and antibacterial activity evaluation of unsaturated aldehydes and diamine condensation derivativesBased on the above study findings,two series of derivatives C and D were further obtained by reductive amination reactions of diamines with unsaturated aromatic aldehydes and unsaturated fatty aldehydes,and the antibacterial activities of these derivatives were evaluated against 10 fungi and 8 bacteria.Compounds C3 and C6showed excellent antibacterial activity against Xanthomonas oryzae pv.oryzae,with MIC of 3.12μg/m L.The preliminary structure-activity relationship showed that the aminated derivatives of 4-Fluorocinnamaldehyde had the best antibacterial activity.3.Preliminary study on the mechanism of high activity compound C3 against Xanthomonas oryzae pv.oryzaeBased on the work in the above two chapters,the high activity compound C3 was used as the test agent to explore the antibacterial mechanism of Xanthomonas oryzae pv.oryzae.The results showed that compound C3 had powerful therapeutic and protective effects against Xanthomonas oryzae pv.oryzae than the control agent Xinjunan at 200μg/m L.The results of scanning electron microscopy（SEM）and transmission electron microscopy（TEM）analysis showed that the cell morphology changed significantly after the treatment of compound C3,and the cell membrane shrank and ruptured,which resulted in a large amount of content leakage.In addition,compound C3 can reduce the pathogenicity of bacteria by inhibiting the secretion of extracellular polysaccharides（EPS）.Meanwhile,the toxicity of compound C3 to Human Embryonic Kidney 293 Cells and Human Liver-7702 was similar to that of Xinjunan,the acute toxicity test showed that the LD₅₀ of compound C3 to mice was245.47 mg/kg,which indicated that compound C3 had moderate toxicity according to the World Health Organization classification standard of oral exogenous toxicity.The above experiments preliminarily indicated that compound C3 could be a candidate compound for new agricultural fungicides.