Study On The Synthesis And Biological Activity Of New ?-carbonyl Amide Derivatives

A series of novel?-ketoamide derivatives was designed and synthesized by using natural product vanillin as starting material and introducing bisamide structure.The structures of the synthesized compounds were characterized by ¹H NMR?¹³C NMR?¹⁹F NMR and HRMS.The bio-activity against tobacco mosaic virus?TMV?,Xanthomonas oryzae pv.oryzae?Xoo?,Ralstonia solanacearum?RS?,and Xanthomonas axonopodis pv.Citri?Xac?was evaluated.The preliminary mechanism of action of active compound was also investigated using molecular docking and transmission electron microscope?TEM?.The innovative findings in this paper was presented as follow:1.39?-ketoamide compounds with novel structure were designed and synthesized.The results of the anti-TMV activity indicated that some compounds have excellent anti-TMV activity.In particular,compound 28 showed the best curative activity(EC₅₀=358.5?g/m L),which was slightly better than that of commercial Ningnanmycin(EC₅₀=362.4?g/m L).The result was verified by in vivo experiments.Moreover,compound 34 shown excellent inactivation on TMV.Preliminary study indicated that fluorine-containing compounds have higher inactivation activity,the more fluorine substituentings in the phenyl group,the higher the anti-TMV activity.2.The antibacterial activity test results showed that the synthesized compounds have good antibacterial activity against Xoo,RS,and Xac.Especially,compounds 2,22,and 33 have good inhibitory activity against RS,and their EC₅₀ values are 35.3?g/m L,38.9?g/m L,and 30.4?g/m L respectively,which are significantly lower than the positive control thiobacillus?99.1?g/m L?.Compound 2 also has a good inhibitory activity against Xac,and the EC₅₀ value is 28.2?g/m L,It is also much lower than the thiobacillus copper?77.1?g/m L?,which shows significantly higher activity than that of positive control thiobacillus.3.Combing the methods of molecular docking and TEM,the interaction between TMV and the active compound 34 was studied based on activity characteristic.The results showed that compound 34 could bind to the key amino acid residues between TMV-CP subunits,affecting TMV particles self-assembly for higher activity against plant virus.