Design, Synthesis, and Antimicrobial Evaluation of Novel Thiazolyl-Based Compounds Incorporating Bioactive Amide and Hydrazide Groups

In recent years, the hydrazide skeleton, as a pivotal class of nitrogen-containing structures, has garnered considerable attention in medicinal chemistry and organic synthesis owing to its unique chemical versatility and broad-spectrum biological activities. In this study, a series of thiazole-containing benzoylhydrazine derivatives A1–A19, B1–B19, and C1–C8 with structural divergence from conventional hydrazide-based molecular frameworks were designed, synthesized, and evaluated for their antifungal/antioomycete activities. The in vitro antifungal/antioomycete assay showed that some of the targeted compounds exhibited remarkable and broad-spectrum antifungal activities. Notably, compounds B10 and C2 exhibited remarkable antifungal activity against Valsa mali (EC50 = 0.790 mg/L for B10; 0.280 mg/L for C2), Sclerotinia sclerotiorum (EC50 = 0.350 mg/L for B10; 1.11 mg/L for C2), and Phytophthora capsici (EC50 = 0.460 mg/L for B10; 0.130 mg/L for C2). The in vivo experiments revealed that compound C2 exhibited excellent control efficacy against P. capsici and V. mali, showing protective and curative activities comparable to those of tebuconazole at an equivalent dose of 40.0 mg/L. Integrated ultrastructural analyses using SEM, TEM, and CLSM revealed that compound C2 compromised hyphal structural integrity in P. capsici and V. mali. In vitro succinate dehydrogenase (SDH) inhibition assays and molecular docking analyses suggest that compound C2 may effectively suppress SDH activity through significant interactions with key amino acid residues at the enzyme’s active site. Furthermore, toxicity tests on Apis Mellifera Ligustica revealed low acute toxicity of B10 and C2 toward A. mellifera L. These results indicate that compound C2 holds potential as a novel antifungal for further investigation.