Discovery of N-((2-Arylthiazol-4-yl)methyl)oxazole-5-carboxamide Derivatives as SDHi for Fungicidal Candidates

A series of oxazole-5-carboxamide derivatives were designed as Succinate Dehydrogenase (SDH) inhibitors and synthesized, characterized, and evaluated for their fungicidal activities. Among these compounds, SEZA18 and SEZC7 displayed 0.17 and 0.50 mg/L EC₅₀ values against Magnaporthe grisea in vitro, respectively, whose anti-M. grisea activities were closed to prochloraz (0.15 mg/L) and surpassed hymexazol (45.5 mg/L). Moreover, SEZA18 and SEZC7 exhibited 45.3 and 49.5% protective effects against M. grisea at the dose of 200 mg/L in vivo, whose preventive effects were about double times less than that of azoxystrobin (93%). In addition, SEZA14 possessed an EC₅₀ value of 2.33 mg/L against Penicillium digitatum in vitro and showed 77.9% prevention effects from P. digitatum at the dose of 100 mg/L in a potted experiment, whose fungicidal activity was comparable to that of boscalid (75.5%). SEZC7 demonstrated SDH inhibitory activity (IC₅₀ = 16.6 μM), exhibiting activity levels similar to those of boscalid (IC₅₀ = 12.9 μM). Molecular docking results further revealed that SEZA14, SEZA18, SEZC7, and boscalid possessed a mode of action similar to that of SDH. Transcriptome analysis suggested that C7 interfered with the energy metabolism by inhibiting SDH activity, thereby affecting cellular sugar metabolism processes of M. grisea. In summary, our finding gave SDH inhibitors featuring novel structures, which provided a potential candidate for the management of plant pathogenic fungi.

design and synthesis; fungicidal activities; molecular docking; oxazole derivatives; succinate dehydrogenase inhibitors.