Succinate dehydrogenase (SDH) is one of the most important molecular targets for the development of new fungicides. Carboxamide fungicides are a class of SDH inhibitors widely used to inhibit highly destructive plant pathogens. Although cases of resistance have been found in fungal pathogens due to the unrestricted use in recent years, there is still demand for new compounds with improved fungicidal activity. Therefore, a series of ester compounds were designed to investigate potential novel antifungal molecules. First, the antifungal activity of different benzyl alcohol compounds (A1-A21) was tested, and a highly active fragment (3,5-dichlorobenzyl alcohol) was found. Subsequently, various compounds were synthesized by esterification between different acids and 3,5-dichlorobenzyl alcohol, among which compound 5 exhibited remarkable antifungal activity against Botrytis cinerea and Rhizoctonia solani with EC50 values of 6.60 and 1.61 mg/L, respectively, which were comparable to those of commercial fungicide boscalid (EC50 = 1.24 and 1.01 mg/L). In vivo testing further demonstrated that compound 5 was effective in suppressing B. cinerea (200 mg/L, 50.9%). Moreover, SDH inhibition assays, fluorescence quenching analysis, and determination of mitochondrial membrane potential revealed that compound 5 has similar effects to boscalid. Furthermore, the fungicidal activity of target compounds can be maintained by modifying the amide bond to an ester bond. These results will provide basis for the development of novel fungicides.
Keywords: 3,5-dichlorobenzyl ester; fungicidal activity; molecular dynamic simulations; succinate dehydrogenase inhibitors.