Discovery of a trans-Configured Monofluoroalkene as a Potent Succinate Dehydrogenase Inhibitor against Phakopsora pachyrhizi

Abstract

A series of monofluoroalkene derivatives were designed and synthesized as succinate dehydrogenase inhibitors (SDHIs). Most compounds showed high in vitro activity against Rhizoctonia solani, with EC₅₀ values below 0.01 mg/L. Compound V-17b (4-OPh) was the most potent (EC₅₀ = 0.0029 mg/L), surpassing boscalid and fluxapyroxad by over 10-fold. Several compounds retained >50% inhibition in vivo at 200 mg/L against Rhizoctonia solani. Compound V-6b exhibited 100% efficacy against Phakopsora pachyrhizi at 1 mg/L, and V-9b showed 77.8% and 96.3% efficacy against Puccinia glumarum and Puccinia sorghi at 10 mg/L, respectively. Enzyme assays revealed that V-9b inhibited porcine SDH (IC₅₀ = 1.87 μM) more effectively than fluxapyroxad (IC₅₀ = 8.13 μM), with the trans isomer superior to the cis. Molecular docking indicated that the trans configuration enables additional π–π stacking with Trp_B173. These results demonstrate that the monofluoroalkene scaffold, combined with appropriate substitution patterns and configuration, can generate potent SDHIs with promising fungicidal profiles.