Design, Synthesis, and Antifungal Activity of Novel Thiophene/Furan-1,3,4-Oxadiazole Carboxamides as Potent Succinate Dehydrogenase Inhibitors

• DOI: 10.1021/acs.jafc.1c03857
• Publication Date: 2021-11-04T20:51:27Z
• Authors: Zihui Yang; Yue Sun; Qingsong Liu; Aliang Li; Wenyan Wang; Wen Gu
• Keywords: Sclerotinia Sclerotiorum; EC50; Furan; Sclerotinia; IC50

Succinate dehydrogenase (SDH) is known as an ideal target for the investigations of fungicides. To develop novel SDH inhibitors, 30 thiophene/furan-1,3,4-oxadiazole carboxamide derivatives were designed and synthesized. In in vitro antifungal assay, a majority compounds demonstrated fair to potent activity against seven tested phytopathogenic fungi. Compounds 4b, 4g, 4h, 4i, 5j showed remarkable Sclerotinia sclerotiorum, affording EC50 values ranging from 0.1∼1.1 mg/L. particular, compound 4i displayed most S. sclerotiorum (EC50 = 0.140 ± 0.034 mg/L), which was superior that boscalid 0.645 0.023 mg/L). A further morphological investigation revealed abnormal mycelia damaged cell structures 4i-treated by scanning electron microscopy. Furthermore, vivo assay 4g effective suppressing rape rot at dosage 200 inhibition also presented significant inhibitory with IC50 1.01 0.21 4.53 0.19 μM, respectively, or equivalent (3.51 2.02 μM). Molecular docking molecular dynamics simulation could form strong interactions key residues SDH. These results indicated this class be promising scaffold discovery development inhibitors.