Discovery of Novel Dual-Functional Phenylthiazole-Benzamide Hybrids as Succinate Dehydrogenase-Inhibiting Fungicides with Promising Phloem Mobility

Abstract

To discover novel phloem-mobile succinate dehydrogenase inhibitor (SDHI) fungicides, 36 phenylthiazole derivatives incorporating amide fragments were designed, synthesized, and evaluated for their antifungal activity. Compound G3 exhibited the highest in vitro activity against Sclerotinia sclerotiorum (EC50 = 0.614 μg/mL), comparable to carbendazim (EC50 = 0.633 μg/mL) and boscalid (EC50 = 0.589 μg/mL). Further investigations revealed that G3 effectively inhibited sclerotial formation and germination, and exhibited remarkable in vivo protective (90.8%) and curative effects (80.3%) at 200 μg/mL. Mechanistic studies using SDH inhibition assays, scanning electron microscopy (SEM), transmission electron microscopy (TEM), molecular docking, and molecular dynamics (MD) simulations demonstrated that G3 shared a similar mode of action with boscalid. Phloem mobility studies demonstrated favorable phloem mobility of these compounds, and G6 as a representative could be efficiently absorbed and distributed in the plants. This study provides a novel strategy for the development of phloem-mobile SDHI fungicides.