Systematic optimizations, antifungal evaluation, mechanism study and potential myosin-5 inhibitor: development of novel cyanoacrylate derivatives bearing phosphate or fluoro fragment.

BACKGROUND

Pesticides are an irreplaceable means of guaranteeing food security. The development of new types of highly efficient, low-toxicity and low-residue pesticides, together with the promotion of pesticide reduction and green developments are important directions of research. Based on this, novel cyanoacrylate derivatives bearing a phosphate or fluoro fragment were synthesized as potential myosin-5 inhibitors using an efficient screening method, namely a stepwise optimization strategy.

RESULTS

A single crystal of compound D11 as a structural representative was scanned using an X-ray diffractometer to further determine its structure. The optimized compound D6 had an excellent half-maximal effective concentration (EC50; 0.40 μg mL-1) in vitro against Fusarium graminearum that was very close to that of the fungicide phenamacril (0.17 μg mL-1). In vivo tests on wheat leaves revealed that compound D6 had outstanding antifungal efficacy. The effect of treatment with optimized compound D6 (25 μg mL-1) on mycelium morphology was demonstrated in a scanning electron microscope experiment, and was consistent with the cell membrane permeability results. Comparisons of the molecular structure and density functional theory calculations revealed that compound D6 had similar thermodynamic and geometrical structure parameters to phenamacril. Furthermore, molecular docking verified that the binding mode between compound D6 and myosin-5 was consistent with phenamacril. The complexes 6UI4-D6 and 6UI4-phenamacril had similar trajectories and close values for total energy and hydrogen bonding.

CONCLUSION

This research constructing novel cyanoacrylate derivatives bearing a phosphate or fluoro fragment as potential myosin-5 inhibitors provides a valuable antifungal lead for development of an efficient fungicide. © 2026 Society of Chemical Industry.