Novel Pyrazole Carboxamide Containing a Diarylamine Scaffold Potentially Targeting Fungal Succinate Dehydrogenase: Antifungal Activity and Mechanism of Action

Abstract

Succinate dehydrogenase (SDH) is known as an ideal target for the development of novel fungicides. Over the years, a series of novel pyrazole carboxamides containing a diarylamine scaffold have been reported as potent SDH inhibitors (SDHIs) in our laboratory. Among them, compound <b>SCU3038</b> (EC₅₀ = 0.016 mg/L) against in vitro <i>Rhizoctonia solani</i> was better than fluxapyroxad (EC₅₀ = 0.033 mg/L). However, its mechanism of action is still unclear. In this paper, in pot tests, bioactivity evaluation indicated that in vivo antifungal activity of compound <b>SCU3038</b> (EC₅₀ = 0.95 mg/L) against <i>R. solani</i> was better than that of fluxapyroxad (EC₅₀ = 2.29 mg/L) and thifluzamide (EC₅₀ = 1.88 mg/L). In field trials, control efficacy of compound <b>SCU3038</b> (74.10%) at 200 g ai/ha against rice sheath blight was better than that of thifluzamide (71.40%). Furthermore, target evaluation showed that compound <b>SCU3038</b> could inhibit the fungal SDH from <i>R. solani</i> and fix in the binding site of SDH by molecular docking, thereby it could dissolve and reduce mitochondria of <i>R. solani</i> as observed by electron microscopy. In addition, transcriptome results showed that compound <b>SCU3038</b> affected the TCA cycle pathway in mitochondria, and this was manifested in the downregulation of eight genes and upregulation of one gene. The most important phenomenon was the repressed expression of SDH2 confirmed by qRT-PCR. It was observed that compound <b>SCU3038</b> was a potent SDHI, and these results afforded further research on pyrazole carboxamides.