Novel amide derivatives containing azetidine moiety as potential SDH inhibitors: Design, synthesis, and evaluation of bioactivity

Abstract

Fluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had obvious antifungal activities against Phomopsis sp., among them, the EC50 value of compound C24 was 5.7 mg/L, which was significantly better than fluopyram (105.4 mg/L). The curative and protective activities of compound C24 on kiwi fruit infected with Phomopsis sp. were 42.2 and 52.9 %, which were better than that of fluopyram (30.4 and 35.6 %) at 200 mg/L. Moreover, compound C24 exhibited excellent inhibitory against SDH. The results of scanning electron microscopy (SEM) indicated that the mycelium of Phomopsis sp. collapsed or even ruptured after compound C24 treatment. Meanwhile, molecular docking showed that compound C24 was deeply embedded into the SDH binding pocket, and the binding model was stabilized by a cation–π interaction with Cys-40, Tyr-58 and an H-bond with Lys-455 and Asn-452. Compound C24 can provide a valuable idea to find new succinate dehydrogenase inhibitors.

Keywords

• Amide containing azetidine
• Bioactivity
• Molecular docking
• SDH inhibitor