Design, synthesis, and antifungal activity of carboxamide derivatives possessing 1,2,3-triazole as potential succinate dehydrogenase inhibitors

Succinate dehydrogenase (SDH) is demonstrably one of the most important molecular targets in development of new fungicide . In our continuous efforts to discover novel SDH inhibitors, forty-two carboxamide derivatives containing 1,2,3-triazole ring were designed and synthesized, which were precisely characterized by 1 H NMR, ESI-MS, elemental analysis and X-ray single-crystal diffraction. The compounds were screened for antifungal activities against phytopathogenic fungi by mycelia growth inhibition assay in vitro. Compound A3-3 exhibited significant antifungal activity against Sclerotinia sclerotiorum , Botrytis cinerea , Rhizoctonia cerealis and Gaeumannomyces graminsis with EC 50 values of 1.08, 8.75, 1.67 and 5.30 μg/mL, respectively, comparable to those of commercial SDHI boscalid. In vivo testing demonstrated that A3-3 was effective for suppressing rape sclerotinia rot, cucumber grey mould and wheat powdery mildew caused by S. sclerotiorum ， B. cinerea and Blumeria graminis at a dosage of 200 μg/mL. Inhibition activities against SDH test proved the designed analogues were effective in the enzyme level. The molecular docking simulation revealed that A3-3 interacted with ARG43，TYR58 and TRP173 of the SDH through hydrogen bond and pi-pi interaction, which could explain the probable mechanism of action between the inhibitor and target protein.