Design, Synthesis, X-ray Crystal Structure, and Agricultural Antifungal Evaluation of Novel Benzohydrazide Derivatives Bearing the Quinazoline Moiety and a Piperazine Linker.

To discover new fungicides, 32 benzohydrazide derivatives incorporating the quinazoline moiety and a piperazine linker were designed and synthesized through a molecular hybridization approach. Among them, the structure of compound A31 was confirmed via X-ray crystallography. The antifungal assays indicated that many derivatives displayed remarkable inhibition activities against the tested fungi, with in vitro EC50 (half-maximal effective concentration) values below 5.0 μg/mL. Particularly, compound A16 demonstrated potent and broad-spectrum inhibition efficacy against seven of the nine fungi, with an average inhibition rate of 96% at 50 μg/mL. Its inhibitory activity against Rhizoctonia solani was impressive, with EC50 = 1.49 μg/mL, roughly comparable to Boscalid (0.84 μg/mL). Aside from the disruption of cytomembrane integrity and the alteration of the mycelial morphology of R. solani by compound A16, this compound could act as a good inhibitor targeting fungal succinate dehydrogenase (SDH) with an IC50 value of 6.83 μg/mL, supported by molecular docking simulations.