Synthesis and Antifungal Activity Evaluation of Novel 2-Cyanoacrylate Derivatives Containing Arylamide Moiety as Potential Myosin-5 Inhibitors

To discover novel compounds with high inhibitory activity and broad-spectrum activity against phytopathogenic fungi, a series of 2-cyanoacrylate derivatives incorporating various types of arylamide moieties were designed and synthesized according to the active substructure splicing principle. The target compounds were structurally characterized by 1H NMR, 13C NMR, HRMS, and X-ray diffraction. Antifungal bioassay revealed that most compounds exhibited significant inhibitory activity against Fusarium graminearum (Fg). The introduction of arylamide groups significantly enhanced antifungal activity against other phytopathogenic fungi while maintaining an excellent inhibition rate against Fg compared to phenamacril. For example, the inhibitory activity of compound G22 against Botrytis cinerea (Bc) and the inhibitory activity of compound G26 against Alternaria solani (As) were significantly better than those of phenamacril. As the most prominent representative, compound G19 presented an EC50 value of 0.326 μg/mL against Fg. Its in vivo curative efficacy on inoculated wheat leaves at 200 μg/mL was comparable to that of the positive control phenamacril. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescence microscopy (FM) revealed that compound G19 severely damaged the surface integrity of mycelial cells and induced cytoplasmic leakage. Molecular docking and molecular dynamics (MD) simulation demonstrated that compound G19 could stably bind to the target protein Myosin-5 in a mode similar to that of phenamacril. This study provides a new idea for the development of novel 2-cyanoacrylate derivatives with antifungal activity.