Design, synthesis and antifungal activity of novel pyrazole-amide-isothiazole derivatives as succinate dehydrogenase inhibitors

Abstract

To discover new fungicides to protect food safety and quality, thirty-four novel pyrazole-amide-isothiazole compounds were designed, synthesised by using scaffold hopping theory for the first time. The bioactivity of all the target compounds against five plant pathogens (Including Penicillium digitatum, Physalospora piricola, Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea) were determined, the results showed that most of the compounds exhibited certain biological activities against B. cinerea in vitro. Compounds 7-XHU-6 had better antifungal activities than fluopyram with the EC₅₀ values were 1.02, 1.78 mg/L, respectively. Moreover, the SDH inhibiting activities results indicated that 7-XHU-6 possessed outstanding activities with an IC₅₀ value of 0.47 mg/L which better than fluopyram (IC₅₀ = 0.88 mg/L). Besides, the in vivo experiments indicated that compound 7-XHU-6 had excellent protection efficiency and therapeutic efficiency. In addition, molecular docking studies demonstrated that compound 7-XHU-6 (-10 kcal/mol) has superior binding energy compared to fluopyram (-8.6 kcal/mol).

Keywords: Antifungal; In vitro; In vivo; Molecular docking; Pyrazole-amide-isothiazole.