Synthesis and Antifungal Activity of 1,2,4-Oxadiazole Derivatives

1,2,4-Oxadiazole derivatives containing anisic acid or cinnamic acid were designed and synthesized, which were expected to be an effective Succinate dehydrogenase (SDH) inhibitor, and their structures were characterized by ¹H NMR, ¹³C NMR, and ESI-MS. The antifungal activity of the compounds against plant pathogenic fungi was screened by the mycelial growth inhibition test in vitro. Compounds <b>4f</b> and <b>4q</b> showed significant antifungal activities against <i>Rhizoctonia solani (R. solani)</i>, <i>Fusarium graminearum (F. graminearum)</i>, <i>Exserohilum turcicum (E. turcicum), Botrytis cinerea (B. cinerea)</i>, and <i>Colletotrichum capsica (C. capsica)</i>. The <i>EC₅</i>₀ values of <b>4q</b> were 38.88 μg/mL, 149.26 μg/mL, 228.99 μg/mL, and 41.67 μg/mL against <i>R. solani</i>, <i>F. graminearum</i>, <i>E. turcicum</i>, and <i>C. capsica</i>, respectively, and the <i>EC</i>₅₀ values of <b>4f</b> were 12.68 μg/mL, 29.97 μg/mL, 29.14 μg/mL, and 8.81 μg/mL, respectively. Compound <b>4f</b> was better than commercial carbendazim against <i>Exserohilum turcicum</i>. Compounds <b>4f</b> and <b>4q</b> showed an antifungal effect on <i>C. capsica</i> of capsicum in vivo. Molecular docking simulation showed that <b>4f</b> and <b>4q</b> interacted with the target protein through the hydrogen bond and hydrophobic interaction, in which <b>4q</b> can form hydrogen bonds with TRP173 and ILE27 of SDH, and <b>4f</b> had hydrogen bonds with TYR58, TRP173, and SER39. This also explains the possible mechanism of action between the inhibitor and target protein.