Design, Synthesis, and Biological Profiles of Novel 1,3,4-Oxadiazole-2-carbohydrazides with Molecular Diversity

To unceasingly expand the molecular diversity of 1,3,4-oxadiazole-2-carbohydrazides, herein, small fragments (including -CH₂-, -OCH₂-, and -SCH₂-) were incorporated into the target compounds to screen out the potential succinate dehydrogenase inhibitors (SDHIs). The bioassay results showed that the antifungal effects (expressed by EC₅₀) against Sclerotinia sclerotiorum, Botryosphaeria dothidea, Fusarium oxysporum, and Colletotrichun higginsianum could reach 1.29 (10a), 0.63 (8h), 1.50 (10i), and 2.09 (10i) μg/mL, respectively, which were slightly lower than those of carbendazim (EC₅₀ were 0.69, 0.13, 0.55, and 0.80 μg/mL, respectively). Especially, compound 10h was extremely bioactive against Gibberella zeae (G. z.) with an EC₅₀ value of 0.45 μg/mL. This outcome was better than that of fluopyram (3.76 μg/mL) and was similar to prochloraz (0.47 μg/mL). In vivo trials against the corn scab (infected by G. z.) showed that compound 10h had control activity of 86.8% at 200 μg/mL, which was better than that of boscalid (79.6%). Further investigations found that compound 10h could inhibit the enzymatic activity of SDH in the G. z. strain with an IC₅₀ value of 3.67 μM, indicating that potential SDHIs might be developed. Additionally, the other biological activities of these molecules were screened simultaneously. The anti-oomycete activity toward Phytophthora infestans afforded a minimal EC₅₀ value of 3.22 μg/mL (10h); compound 4d could strongly suppress the growth of bacterial strains Xanthomonas axonopodis pv. citri and Xanthomonas oryzae pv. oryzae with EC₅₀ values of 3.79 and 11.4 μg/mL, respectively; and compound 10a displayed some insecticidal activity toward Plutella xylostella. Given their multipurpose features, these frameworks could be actively studied as potential pesticide leads.