Discovery of <i>N</i>-((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, <b>SEZA18</b> and <b>SEZC7</b> displayed 0.17 and 0.50 mg/L EC₅₀ values against <i>Magnaporthe grisea</i> in vitro, respectively, whose anti-<i>M. grisea</i> activities were closed to prochloraz (0.15 mg/L) and surpassed hymexazol (45.5 mg/L). Moreover, <b>SEZA18</b> and <b>SEZC7</b> exhibited 45.3 and 49.5% protective effects against <i>M. grisea</i> at the dose of 200 mg/L <i>in vivo,</i> whose preventive effects were about double times less than that of azoxystrobin (93%). In addition, <b>SEZA14</b> possessed an EC₅₀ value of 2.33 mg/L against <i>Penicillium digitatum</i> in vitro and showed 77.9% prevention effects from <i>P. digitatum</i> at the dose of 100 mg/L in a potted experiment, whose fungicidal activity was comparable to that of boscalid (75.5%). <b>SEZC7</b> 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 <b>SEZA14</b>, <b>SEZA18</b>, <b>SEZC7</b>, and boscalid possessed a mode of action similar to that of SDH. Transcriptome analysis suggested that <b>C7</b> interfered with the energy metabolism by inhibiting SDH activity, thereby affecting cellular sugar metabolism processes of <i>M. grisea</i>. In summary, our finding gave SDH inhibitors featuring novel structures, which provided a potential candidate for the management of plant pathogenic fungi.