Exploration of Fungicidal Activity and Mode of Action of Ferimzone Analogs.

Lead discovery and molecular target identification are important for developing novel pesticides. Scaffold hopping, an effective approach of modern medicinal and agrochemical chemistry for a rational design of target molecules, is aiming to design novel molecules with similar structures and similar/better biological performance. Herein, 24 new ferimzone derivatives were designed and synthesized by a scaffold-hopping strategy. In vitro bioassays indicated that compound showed similar potency to ferimzone against and 2-fold higher potency than ferimzone against . Compounds , , and displayed fungicidal activity with EC values ranging from 1.17 to 3.84 μg/mL against , and compounds and displayed 1.6-1.8-fold higher activity than ferimzone against . The in vivo bioassays at 200 μg/mL indicated that compound was more potent than ferimzone against (90% vs 70% efficacy, respectively). Density functional theory (DFT) calculations elucidated the structure-energy relationship. Although the mode of action of ferimzone is still unclear, studies suggested that compound significantly inhibited the growth and reproduction of , and its energy metabolism pathways (e.g., starch, sucrose, lipids, and glutathione) were seriously downregulated after a treatment.