The Design, Synthesis And Antibacterial Activity Of 1,3,4-oxadiazole Sulfone Compounds Containing 3,4-dichloroisothiazolamide Structure

In this study,a series of 1,3,4-oxadiazole sulfone derivatives containing the chloroisothiazolylamide moiety was synthesized.Then,their antibacterial activities against the rice leaf blight?Xanthomonas oryzae pv.oryzae?Xoo??and rice bacterial streak?Xanthomonas oryzae pv.oryzicola?Xoc??were evaluated.Lastly,preliminary mechanisms of the target compounds with high antibacterial activity were studied.The conclusion followed as below:With mesotriazole as the lead structure and,an active skeleton of3,4-dichloroisothiazolylamide was introduced based on the principle of active substructure splicing.Thirty 1,3,4-oxadiazole sulfone compounds containing3,4-dichloroisothiazolylamide moiety were designed and synthesized.High-resolution mass spectrometry?HRMS?characterized the structures of target compounds.The turbidity method was used to test the antibacterial activities with Xanthomonas oryzae pv.oryzae and Xanthomonas oryzae pv.oryzicola as the examined object.The antibacterial activities of the target compounds were evaluated at 50?g/mL and 10?g/mL,respectively.Some of the compounds showed good antibacterial activity against Xanthomonas oryzae pv.oryzae.Among them,the EC₅₀of compounds 2 and 3 against Xanthomonas oryzae pv.oryzae were 0.79 and 0.85?g/mL,respectively,which were significantly lower than those of the control agents bismerthiazol(EC₅₀=72.13?g/m L),thiodiazole copper(EC₅₀=91.15?g/mL)and isotianil(EC₅₀=35.90?g/mL).Results under greenhouse condition showed that the protection and curative efficacy of compound 2 at a concentration of 50?g/mL against Xanthomonas oryzae pv.oryzae were 43.99%and 41.06%,respectively,which were superior to the commercial agents bismerthiazol?31.20%and 37.12%?,thiodiazole copper?28.00%and 29.03%?and isotianil?15.19%and 13.41%?.Study on the preliminary antibacterial mechanism of compound 2 against Xanthomonas oryzae pv.Oryzae was carried out.The shake flask fermentation method was used to study the effect of compound 2 on the extracellular polysaccharide of the pathogen.At the concentrations of 3.2,1.6,and 0.8?g/mL,the inhibitory rates of compound 2 on the extracellular polysaccharide of rice leaf blight were 91.48%,46.60%and 18.13%,respectively;which showed that compound 2 may reduce the pathogenic capacity of the bacteria.After treatment with the compound 2at the concentrations of 3.2,1.6,and 0.8?g/mL,the relative permeability of Xanthomonas oryzae pv.oryzae cell membrane increased with the increase in the concentration and time,thereby indicating that compound 2 can change the permeability of the cell membrane of the bacterial blight bacteria to disrupt the normal growth of the bacteria.Addtionally,cells of rice blight pathogen treated with different concentrations of compound 2 have deformed,shrunk,and cracked to vary degrees,indicating that compound 2 can destroy the cell structure of Xanthomonas oryzae pv.oryzae to influence the normal physiological metabolism of the fungus and inhibits the growth and reproduction of the fungus.