Design, Synthesis, Antifungal Activity, and Mechanism of Action of New Piperidine-4-carbohydrazide Derivatives Bearing a Quinazolinyl Moiety.

A series of new piperidine-4-carbohydrazide derivatives bearing a quinazolinyl moiety were prepared and evaluated for their fungicidal activities against agriculturally important fungi. Among these derivatives, the chemical structure of compound was clearly verified by X-ray crystallographic analysis. The antifungal bioassays revealed that many compounds in this series possessed good to excellent inhibition effects toward the tested fungi. For example, compounds and had EC values of 0.83 and 0.88 μg/mL against , respectively, superior to those of positive controls Chlorothalonil and Boscalid (1.64 and 0.96 μg/mL, respectively). Additionally, the above two compounds also exhibited notable inhibitory activities against (with EC values of 1.12 and 3.20 μg/mL, respectively), far better than the positive controls Carbendazim and Chlorothalonil (19.3 and 11.0 μg/mL, respectively). More importantly, compound could potently inhibit the proliferation of in the potted rice plants, showing good curative and protective efficiencies of 76.9% and 76.6% at 200 μg/mL, respectively. Furthermore, compound demonstrated an effective inhibition of succinate dehydrogenase (SDH) activity with an IC value of 6.07 μM. Finally, the molecular docking study revealed that this compound could be well embedded into the active pocket of SDH via multiple noncovalent interactions, involving residues like SER39, ARG43, and GLY46.