Design, synthesis and antifungal activity of novel thiazole sulfonamide derivatives bearing piperidine moiety

To develop novel fungicidal candidates, 45 novel thiazole sulfonamide derivatives bearing piperidine moieties were rationally designed and synthesized via active substructure splicing. Bioassay results revealed that compound 3a-24 exhibits the optimal antifungal potency against Sclerotinia sclerotiorum, with an EC 50 value of 1.25 mg/L, superior to thifluzamide (1.36 mg/L). Compound 3a-24 also exerted moderate inhibitory effect on sclerotia formation and germination. In vivo protective and curative efficacies of compound 3a-24 on rapeseed seedlings reached 81.1% and 63.2%, respectively, exceeding thifluzamide (59.2%, 56.3%), comparable to fluxapyroxad (83.9%, 67.8%), yet inferior to boscalid (95.8%, 70.1%). In vitro enzyme inhibition activity assay indicated that compound 3a-24 strongly inhibits succinate dehydrogenase of S. sclerotiorum ( Ss SDH), with an IC 50 value of 1.32 mg/L. Binding affinity determination combined with molecular docking proved that compound 3a-24 could stably bind to the key active site of Ss SDH. Furthermore, the defense enzyme assay indicated that compound 3a-24 could regulate the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) of oilseed rape, implying its capacity to trigger plant disease resistance. Collectively, these results revealed that this kind of thiazole sulfonamide derivatives could serve as promising succinate dehydrogenase inhibitor (SDHI) fungicides for the management of S . sclerotiorum .