关键词: 噁唑菌酮, 噁唑烷二酮, 抑菌活性, 构效关系, 分子对接

Abstract: A series of novel oxazolidinedione derivatives (2-2 to 2-30) were designed and synthesized based on the structure of pyramoxadone, a 5-position pyridine analogue of famoxadone. The target compounds were characterized by 1H NMR, 13C NMR, and HRMS. Their in vitro antifungal activities were evaluated against nine plant pathogenic fungi using the mycelial growth rate method, with famoxadone as a positive control. Preliminary screening at 50 mg/L revealed that most compounds exhibited moderate to excellent inhibitory activity, particularly against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, and Pyricularia grisea. Structure-Activity Relationship (SAR) analysis indicated that bulky groups such as tert-butyl and cyclohexyl are detrimental to the enhancement of antifungal activity, while fluorine-containing compounds generally exhibited enhanced antifungal activity. Compounds 2-16 (EC50 = 3.78 mg/L) and 2-26 (EC50 = 1.61 mg/L) exhibited superior activity against R. solani compared to famoxadone (EC50 = 4.38 mg/L) and pyramoxadone (EC50 = 9.67 mg/L). In vivo protective efficacy assays demonstrated that compounds 2-13, 2-16, and 2-18 provided 88.3%, 89.5%, and 81.7% control against cotton damping-off at 200 mg/L, respectively, significantly outperforming the positive control. Molecular docking and electrostatic surface map analysis revealed that the structure-activity relationship of this class of compounds follows a pattern where the hydrophobic skeleton determines the binding orientation, electrostatic complementarity determines the binding strength, and substituent fine-tuning determines the activity level.

Key words: Famoxadone; Oxazolidinedione, Antifungal activity, Structure-activity relationship, Molecular docking