Design, Synthesis and Anti-fungal Activity of 1,2,4-Oxadiazole Derivatives Containing Diamide Moiety

To search the novel and efficient antifungal lead compounds, twenty-seven 1,2,4-oxadiazole derivatives (compounds 4a -4c and 6a-6x) containing diamide moiety with novel chemical structures were designed and synthesized, which was based on the method of the splicing of bioactive substructures. The structures of target compounds were characterized by means of 1H NMR and HRMS spectra. The bioassay results showed that, at the concentration of 3.13 mg/L, the control effect of compounds 6f, 6i, 6m, 6n and 6q against Soybean rust(Phakopsora- pachyrhiz) were 80%, 90%, 80%, 90% and 70%, respectively. The above activities were all better than Flufenoxa- diazam(30%) and the control agent Difenoconazole(50%). Compound 6n also showed prominent antifungal activity against Corn rust(Pucciniasorghi), which control effect was 100% at the concentration of 1.56 mg/L. The molecular docking simulation revealed that compound 6n has various interactions with histone deacetylase 4(HDACs 4),which compound 6n interacts with PRO-298, LEU-299 and HIS-158 through hydrogen bond may be the important source why it showed prominent antifungal activity.